Abstract
Lead (Pb) is a toxic heavy metal and can harm organisms by inducing apoptosis. Selenium (Se), an essential trace element for humans and animals, can alleviate heavy metal toxicity. The aim of our study is to investigate alleviative effect of Se on Pb-induced apoptosis via endoplasmic reticulum (ER) stress in chicken kidneys. One hundred and eighty male chickens were randomly divided into four groups at 7 days of age and were fed with commercial diet (containing 0.49 mg/kg Se) and drinking water, Na2SeO3-added commercial diet (containing 1 mg/kg Se) and drinking water, the commercial diet and (CH3OO)2Pb-added drinking water (containing 350 mg/L Pb), and Na2SeO3-added commercial diet (containing 1 mg/kg Se) and (CH3OO)2Pb-added drinking water (containing 350 mg/L Pb), respectively. On the 30th, 60th, and 90th days of the experiment period, 15 chickens in each group were euthanized and the kidneys were collected. Following contents were performed: kidney ultrastructure; nitric oxide (NO) content; inducible nitric oxide synthase (iNOS) activity; relative messenger RNA (mRNA) and protein expression of iNOS, ER-related genes (glucose-regulated protein (GRP)78, GRP94, activating transcription factor (ATF)4, ATF6, and iron-responsive element (IRE)), and apoptosis-related genes (caspase-3 and B cell lymphoma-2 (Bcl-2)); and caspase-12 protein expression. The results indicated that Pb changed kidney ultrastructural structure; decreased Bcl-2 mRNA and protein expression; and increased NO content, iNOS activity, relative mRNA and protein expression of iNOS, ER-related genes, and caspase-3 and caspase-12 protein expression. Se attenuated above changes caused by Pb. Pb had time-dependent manners on NO content, GRP78, GRP94, ATF4, IRE, and caspase-3 mRNA expression. Se attenuated Pb-induced apoptosis via ER stress in the chicken kidneys.
Similar content being viewed by others
Explore related subjects
Discover the latest articles, news and stories from top researchers in related subjects.Avoid common mistakes on your manuscript.
Introduction
Lead (Pb) could cause water and soil pollution, and then affected the health of humans and animals, even affected biodiversity in wild birds through Pb accumulation in food chains. In the Ludhiana, Jalandhar, and Malerkotla areas of India, industrial activities caused Pb pollution in waters and soils and Pb accumulation in cabbages, cauliflowers, and Indian mustard [1]. In some provinces of China, such as Yunnan, Guizhou, and Sichuan, Pb pollution in waters, soils, vegetables, and crops caused by mining activities led to high blood Pb level, malacosteon, and kidney damage in local children [2]. In Pyeongtaek, Korea, the cumulation of inorganic fertilizer and pesticide led to Pb accumulation in gray herons, intermediate egrets, and black-crowned night herons, and seven of the birds even died [3]. Pb poisoning was an important cause of death in endangered white-headed ducks (Oxyura leucocephala) and swans (Cygnus sp.) [4]. The kidney is a target organ of Pb toxicity. Exposure to Pb led to damage in the kidneys of rats [5] and chickens [6]. Some researchers found that Pb-induced apoptosis was a probable mechanism of Pb toxicity. Pb exposure induced apoptosis in chicken erythrocytes [7] and rat proximal tubular cells [8, 9].
A large amount of nitric oxide (NO) can cause apoptosis [10]. Inducible nitric oxide synthase (iNOS) can synthesize NO. In some cell types, endoplasmic reticulum (ER) stress pathway is involved in NO-induced apoptosis [10]. Glucose-regulated protein (GRP)78, GRP94, activating transcription factor (ATF)4, ATF6, and iron-responsive element (IRE) are involved in ER stress [11]. caspase-12 is an apoptosis gene and is located on the ER. The activation of caspase-12 could cause the activation of caspase-3, and then cause apoptosis [12]. NO long-lasting production can promote apoptosis by altering Bcl-2 family proteins and caspase family proteases [13]. Excess Pb upregulated NO content and iNOS activity in chicken livers [14]. Mingwei Xing found that arsenic (As) induced iNOS messenger RNA (mRNA) and protein expression in chicken gastrointestinal tracts [15]. Excess Pb can increase NO content in rat kidneys [5], GRP78 protein expression in rat astrocytes [16], caspase-3 activity in rat kidneys [5], and caspase-3 protein expression in rat livers [17]; decrease Bcl-2 protein expression in the kidneys [5] and livers [17] of rats; and cause apoptosis in the kidneys [5] and livers [17] of rats.
Selenium (Se) is an essential trace element for animals [18] and is involved in various biological processes [19, 20]. Se can antagonize toxicity induced by heavy metals, such as mercury in K-562 cells [21] and in residents [22], cadmium (Cd) in chicken livers [23], and Pb in chicken bursa of Fabricius [24]. Se alleviated Pb-induced iNOS mRNA and protein expression in chicken neutrophils [25], Cd-induced ER stress in chicken kidneys [26] and neutrophils [27], and apoptosis in chicken livers [23] and neutrophils [27]. However, alleviative effect of Se on Pb-induced apoptosis via ER stress in chicken kidneys has not yet been completely understood. Therefore, we designed the experiment to investigate alleviative effect of Se on Pb-induced apoptosis via ER stress in chicken kidneys.
Materials and Methods
Animal Model
One hundred and eighty 1-day-old Hyline male chickens were fed a commercial diet with 0.49 mg/kg Se and drinking water for 7 days. The chickens were randomly divided into four groups: the control group, the Se group, the Pb group, and the Se/Pb group. The chickens in the control group were fed a commercial diet and drinking water. The chickens in the Se group were fed Na2SeO3·5H2O (analytical reagent grade, Tianjin, Zhiyuan Chemical Reagent Co. Ltd., Tianjin, China) plus a commercial diet containing 1 mg/kg Se and drinking water. The chickens in the Pb group were fed a commercial diet and (CH3OO)2Pb·3H2O (analytical reagent grade, Tianjin, China) plus drinking water contaminated with 350 mg/L Pb. The use of Pb dose was conducted in the needs of experiment toxicology [28], according to a median lethal does (LD50) of Pb for chickens [29]. The chickens in the Se/Pb group were fed Na2SeO3·5H2O plus a commercial diet containing 1 mg/kg Se and (CH3OO)2Pb·3H2O plus drinking water contaminated with 350 mg/L Pb. The chickens were maintained in the Laboratory Animal Center, College of Veterinary Medicine, Northeast Agricultural University (Harbin, China). Food and water were provided ad libitum for chickens during the entire experimental period. All procedures used in this experiment were approved by the Northeast Agricultural University’s Institutional Animal Care and Use Committee under the approved protocol number SRM-06.
Tissue Sample Collection
Fifteen chickens were randomly selected from four groups, and then euthanized on the 30th, 60th, and 90th days of the experiment, respectively. The kidneys were immediately excised and washed with ice-cold 0.9% NaCl solution. Every kidney tissue was divided into three parts. One part was fixed with 2.5% glutaraldehyde phosphate-buffered saline (v/v, pH 7.2) for ultrastructure observation. One part was homogenized to detect NO content and iNOS activity. The last part was frozen in liquid nitrogen and stored in a −80 °C refrigerator for quantitative real-time polymerase chain reaction (PCR) and Western blot.
Ultrastructure Observation
On the 90th day of the experiment, the kidney tissues from four groups were cut into small blocks (1.0 mm × 1.0 mm × 1.0 mm). These blocks were stained using 2.5% glutaraldehyde in 0.1 M sodium phosphate buffer (v/v, pH 7.2) at 4 °C for 3 h, and 1% osmium tetroxide (v/v) at 4 °C for 1 h. Then the tissues were dehydrated in graded series of ethanol (50, 70, 90, and 100% ethanol for 10 min, respectively). The samples were embedded with epoxy resins and cut into ultrathin sections. The ultrathin sections were impregnated in magnesium-uranyl acetate and Pb citrate. Kidney ultrastructure was observed under a transmission electron microscope.
NO Content and iNOS Activity
NO content and iNOS activity were measured using NO and iNOS detection kits according to the manufacturer’s instructions (Nanjing Jiancheng Bioengineering Institute, Nanjing, China).
Relative mRNA Expression of iNOS, GRP78, GRP94, ATF4, ATF6, IRE, Bcl-2, and caspase-3
Primer Sequences
The specific primers of iNOS, GRP78, GRP94, ATF4, IRE, ATF6, Bcl-2, caspase-3, and β-actin published in GenBank are shown in Table 1. β-actin was used as an internal reference gene. The primers were synthesized by Invitrogen Biotechnology Co. Ltd. (Shanghai, China).
Total RNA Extraction and Reverse Transcription
Total RNA was extracted from kidney tissues using RNAiso Plus reagent according to the manufacturer’s instructions (Takara, Japan). The concentration and purity of the total RNA were determined using GeneQuant 1300 spectrophotometer (Healthcare Bio-Sciences AB, Sweden) at 260/280 nm. The total RNA was immediately used to synthesize complementary DNA (cDNA). Reverse transcription (RT) reaction system (60 μL) (Haigene, China) contained 6 μL of total RNA, 1.5 μL of RNase inhibitor (40 U/μL), 3 μL of dNTP mixture (10 mM each), 6 μL of 10 × RT buffer, 3 μL of golden MLV reverse transcriptase, 3 μL of 20 × oligo dT (25) and random primer, and 37.5 μL of RNase-free H2O. The reaction conditions were at 30 °C for 15 min, at 55 °C for 50 min, and at 80 °C for 10 min. The synthesized cDNA was diluted five times with sterile water and then was stored in a −20 °C refrigerator for real-time quantitative PCR.
Real-time Quantitative PCR
Real-time quantitative PCR was performed using LightCycler®96 Real-Time PCR System according to the manufacturer’s instructions (Roche Life Science, Shanghai, China). The reaction system (10 μL) consisted of 1 μL of cDNA, 3.4 μL of sterile distilled water, 5 μL of 2 × SYBR green PCR master mix (Takara, China), 0.3 μL of forward primer (10 μM), and 0.3 μL of reverse primer (10 μM). The PCR reaction program was at 95 °C for 10 min, degeneration at 95 °C for 2 min, 40 cycles at 95 °C for 15 s, and at 60 °C for 1 min. Every sample was measured three times. The melting curve analysis showed only one peak for each PCR product. Relative mRNA abundance was calculated according to the method of Pfaffl [30].
Western Blot Analysis
The proteins of iNOS, GRP78, GRP94, ATF4, ATF6, IRE, caspase-12, Bcl-2, and caspase-3 were extracted on the 90th day in sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. SDS-polyacrylamide gel (containing H2O, 30% acrylamide mix, Tris-Hcl buffer (pH 8.8), 20% SDS, 20% 2-aminophenol 4-sulfonic acid, and N,N,N′,N′-tetramethylethylenediamine) was prepared according to molecular size of proteins. The concentration of 30% acrylamide mix in SDS-polyacrylamide gel was 10% for iNOS; 12% for caspase-12, Bcl-2, and caspase-3; and 15% for GRP78, GRP94, ATF4, ATF6, and IRE, respectively. Proteins were separated and transferred onto nitrocellulose membranes in a tank transfer apparatus (containing Tris-glycine buffer and 20% methanol) at 100 mA for 1 h. The membranes were blocked with 5% nonfat milk at 4 °C overnight. The membranes were incubated at 37 °C for 2 h with the diluted primary antibodies iNOS (1:500), GRP78 (1:500), GRP94 (1:500), ATF4 (1:600), ATF6 (1:600), IRE (1:600), caspase-12 (1:200), Bcl-2 (1:500), and caspase-3 (1:100), respectively. After being washed for a third time (15 min each time) with phosphate-buffered saline (containing 10 mM Tris-HCl (pH 7.6), 100 mM NaCl, and 0.1% Tween 20), the membranes were incubated at 37 °C for 1 h with peroxidase-conjugated secondary antibodies against rabbit IgG (1:1000, Santa Cruz, USA) and were washed thrice (15 min each time) with the phosphate-buffered saline again. The signal was detected using X-ray films (TransGen Biotech Co., Beijing, China). The optical density was measured using Image VCD gel imaging system (Beijing Sage Creation Science And Technology Co. Ltd., Beijing, China).
Statistical Analysis
Statistical analysis was performed using SPSS for Windows (version 17.0; SPSS Inc., Chicago, IL, USA) in two-way ANOVA for the kit data and mRNA expression, and in one-way ANOVA for the protein expression data. All results were expressed as the mean ± standard deviation. The comparisons of results were verified by nonparametric Kruskal-Wallis ANOVA and Mann-Whitney U tests. Different uppercase letters were significantly different (P < 0.05) among different time points in the same group. Different lowercase letters were significantly different (P < 0.05) among different groups at the same time point.
Results
Ultrastructure Observation
Kidney histological study was used in our experiment as shown in Fig. 1. The cells in the control (Fig. 1(a)) and Se (Fig. 1(b)) groups showed a clear cell nucleus (N), a homogeneous cytoplasm, and an intact mitochondria (MI). The cells in the Pb group showed shrinkage of cytoplasm and chromatin (Fig. 1(c)), small cell size (Fig. 1(c)), nuclear chromatin agglutination (Fig. 1(d)), and ER amplification (Fig. 1(d)). The cells in the Se/Pb group showed densely stained nuclei, partial margination of chromatin (Fig. 1(e)), and ER amplification (Fig. 1(e and f)).
NO Content, iNOS Activity, and iNOS mRNA and Protein Expression
NO content (Fig. 2 (a)), iNOS activity (Fig. 2 (b1)), and iNOS mRNA expression (Fig. 2 (b2)) for 30, 60, and 90 days and iNOS protein expression (Fig. 2 (b3)) for 90 days in chicken kidneys from four groups are shown in Fig. 2. There were no significant differences (P > 0.05) of NO content, iNOS activity, and iNOS mRNA expression at all three time points and iNOS protein expression between the control group and the Se group. Compared with the control, Se, and Se/Pb groups, all above indexes increased significantly (P < 0.05) in the Pb group. Compared with the control and Se groups, all above indexes increased significantly (P < 0.05) in the Se/Pb group except iNOS mRNA expression for 30 days. NO content and iNOS mRNA expression increased significantly (P < 0.05) with the increase of time in the Pb group. iNOS activity for 60 and 90 days was significantly higher (P < 0.05) than that for 30 days in the Pb group.
Relative mRNA and Protein Expression of ER-related Genes
We detected relative mRNA expression for 30, 60, and 90 days and protein expression for 90 days of ER-related genes (GRP78 (Fig. 3 (a1 and a2)), GRP94 (Fig. 3 (b1 and b2)), ATF4 (Fig. 3 (c1 and c2)), ATF6 (Fig. 3 (d1 and d2)), and IRE (Fig. 3 (e1 and e2))) to investigate alleviative effect of Se on Pb-induced apoptosis via ER stress in chicken kidneys. Our results showed that there were no significant differences (P > 0.05) of all above genes on all the time points between in the control group and in the Se group. Relative mRNA and protein expression of the five ER-related genes in the Pb group was significantly higher (P < 0.05) than that in the control, Se, and Se/Pb groups except GRP78 mRNA expression for 30 days and IRE protein expression in the Se/Pb group. Relative mRNA and protein expression of the five ER-related genes in the Se/Pb group was significantly higher (P < 0.05) than that in the control and Se groups except mRNA expression of ATF6 for 60 days and IRE for 30 days, and protein expression of GRP94 and ATF4. Relative mRNA expression of GRP78, GRP94, ATF4, and IRE increased significantly (P < 0.05) with the increase of time in the Pb group. ATF6 mRNA expression for 90 days was significantly higher (P < 0.05) than that for 30 and 60 days in the Pb group.
Relative mRNA and Protein Expression of Apoptosis-related Genes
As shown in Fig. 4, protein expression of caspase-12 (Fig. 4 (a)) and mRNA and protein expression of Bcl-2 (Fig. 4 (b1 and b2)) and caspase-3 (Fig. 4 (c1 and c2)) were detected in chicken kidneys. We found that there were no significant differences (P > 0.05) of mRNA and protein expression of all above genes between the control group and the Se group. caspase-12 protein expression and caspase-3 mRNA and protein expression in the Pb group were significantly higher (P < 0.05) than those in the control, Se, and Se/Pb groups. caspase-12 protein expression and caspase-3 mRNA and protein expression in the Se/Pb group were significantly higher (P < 0.05) than those in the control and Se groups. In contrast, Bcl-2 mRNA and protein expression in the Pb group was significantly lower (P < 0.05) than that in the control, Se, and Se/Pb groups. Bcl-2 mRNA and protein expression in the Se/Pb group was significantly lower (P < 0.05) than that in the control and Se groups. caspase-3 mRNA expression increased significantly (P < 0.05) with the increase of time in the Pb group. Bcl-2 mRNA expression for 60 and 90 days was significantly lower (P < 0.05) than that for 30 days in the Pb group.
Discussion
Pb pollution led to Pb poisoning in wild birds. Rafael Mateo and Ronda de Toledo [4] found that 17 species of birds of prey suffered Pb poisoning in Europe, and some of them were near threatened, such as the white-tailed eagle (Haliaeetus albicilla), or endangered, such as the Spanish imperial eagle (Aquila adalberti). In eastern Poland, very high Pb concentration was found in birds in hunting areas [31]. Zhang et al. [16] found that Pb poisoning increased GRP78 protein expression in rat astrocyte cells. Pb exposure promoted caspase-3 activity in the rat proximal tubular cells [32]. ER stress can induce apoptosis [33]. Therefore, we detected GRP78, GRP94, ATF4, ATF6, IRE, Bcl-2, and caspase-3 mRNA and protein expression and caspase-12 protein expression to investigate Pb-induced apoptosis via ER stress in chicken kidneys.
NO plays roles both in physiological and pathophysiological consequences [34]. NO is produced by iNOS. iNOS catalyzed overproduction of NO [35]. GRP78 was highly upregulated in NO-generating cells [34]. GRP78 and GRP94 are ER chaperonins and play major roles in ER integrity [36]. ATF6 and IRE1 are two of three types of ER membrane receptors and may sense stress in ER and eventually activate transcription factors for induction of GRP78 [37]. ATF6, an ER stress-regulated transmembrane transcription factor, binds GRP78 and dissociate in response to ER stress [38]. ATF4 can activate the GRP78 promoter independent of ER stress elements [39]. ER stress activated ER-resident caspase-12 [40] which may play a role in apoptosis after ER stress [41]. caspase-12 indirectly activated cytoplasmic caspase-3, and finally induced neuronal apoptosis [41]. Bcl-2-related proteins are located on the ER membrane [42]. NO produced by astrocytes after hypoxic insult downregulated Bcl-2, and then activated caspase-3, induced apoptotic death of neurons [43]. In our experiment, we found that excess Pb increased GRP78, GRP94, ATF4, ATF6, IRE, and caspase-3 mRNA and protein expression; increased caspase-12 protein expression; and decreased Bcl-2 mRNA and protein expression in chicken kidneys. Our finding indicated that excess Pb induced ER stress and apoptosis in chicken kidneys. Consistent with our results, other researchers also found that Pb, Cd, and As could induce ER stress and apoptosis. Excess Pb induced GRP78 and GRP94 protein expression, induced ATF4 mRNA expression, and caused ER stress and apoptosis in bovine aortic endothelial cells [44]. Excess Cd upregulated GRP78 and GRP94 mRNA expression, and caused ER stress and apoptosis in chicken hepatocytes [45]. Cd exposure increased NO content; increased iNOS activity; increased iNOS, GRP78, GRP94, ATF4, ATF6, IRE, and caspase-3 mRNA expression; decreased Bcl-2 mRNA expression; and caused ER stress and apoptosis in chicken kidneys [26]. Chen et al. found that excess Cd increased NO content; increased iNOS activity; increased GRP78, ATF6, caspase-12, and caspase-3 mRNA expression; increased caspase-12 protein expression; and caused ER stress and apoptosis in chicken neutrophile granulocytes [27]. Excess As caused apoptosis via ER stress by inducing the mRNA and protein expression of GRP78 and GRP94; inhibiting Bcl-2 protein expression; and increasing caspase-3 and caspase-12 activities in mouse osteoblasts [46]. Our morphological study also demonstrated that Pb poisoning led to apoptosis in chicken kidneys. Other morphological researches were similar with our results. Excess Pb induced apoptosis in chicken kidneys [6] and rat brain hippocampi [47]. In addition, we also found that Pb had time-dependent manners on NO content and iNOS, GRP78, GRP94, ATF4, IRE, and caspase-3 mRNA expression in chicken kidneys. Shinkai et al. [44] also found that Pb increased GRP78 and GRP94 protein expression in a time-dependent manner in bovine aortic endothelial cells.
Se could alleviate Pb and Cd poisoning by decreasing NO, iNOS, GRP78, GRP94, ATF4, ATF6, IRE, caspase-12, and caspase-3 and increasing Bcl-2. Se alleviated the increase of NO content, iNOS activity, and iNOS mRNA and protein expression in chicken testes [48]; decrease of Bcl-2 mRNA and protein expression; increase of caspase-3 mRNA and protein expression; and apoptosis induced by Pb in chicken kidneys [6]. Liu et al. [26] reported that Se alleviated increase of NO content, iNOS activity, and iNOS, GRP78, GRP94, ATF4, ATF6, IRE, and caspase-3 mRNA expression; decrease of Bcl-2 mRNA expression; and ER stress caused by Cd in chicken kidneys. Se also alleviated increase of NO content, iNOS activity, GRP78, ATF6, caspase-12, caspase-3 mRNA expression, and caspase-12 protein expression; and apoptosis via ER stress caused by Cd in the neutrophils of chickens [27]. Se supplementation protected against increase of NO content, iNOS activity, and caspase-3 mRNA expression; decrease of Bcl-2 mRNA expression; and apoptosis caused by Cd in chicken livers [23]. Therefore, we investigated the alleviative effect of Se on Pb-induced apoptosis via ER stress in chicken kidneys. Similar results were obtained in our study. In our experiment, we found that Se alleviated the increase of NO content, iNOS activity, iNOS, GRP78, GRP94, ATF4, ATF6, IRE, caspase-3 mRNA expression, and caspase-12 protein expression and the decrease of Bcl-2 mRNA expression caused by Pb in chicken kidneys. Our results indicated that Se alleviated Pb-induced apoptosis via ER stress in chicken kidneys. The ultrastructural observation of our study also indicated that Se alleviated Pb-induced ultrastructure changes and Pb-induced apoptosis in chicken kidneys. Zhang et al. [23] also found that Se alleviated Cd-induced ultrastructural changes and Cd-induced apoptosis in chicken livers.
Pb pollution led to Pb poisoning in wild birds and even impacted biodiversity of wild birds. Therefore, chickens were used as experimental animals to investigate toxic effect of Pb and alleviative effect of Se on Pb toxicity in our experiment. The results of our experiment indicated that excess Pb caused ultrastructure changes, upregulated NO content, iNOS activity, iNOS, GRP78, GRP94, ATF4, ATF6, IRE, caspase-3 mRNA and protein expression, and caspase-12 protein expression, and downregulated Bcl-2 mRNA and protein expression. Se alleviated all the above changes caused by Pb. There were time-dependent effects on NO content, iNOS, GRP78, GRP94, ATF4, IRE, and caspase-3 mRNA expression. Se alleviated Pb-induced apoptosis via ER stress in chicken kidneys.
References
Sikka R, Nayyar VK (2009) Monitoring of lead (Pb) pollution in soils and plants irrigated with untreated sewage water in some industrialized cities of Punjab, India. Environ Monit Assess 154(4):53–64. doi:10.1007/s10661-008-0377-4
Zhang X, Yang L, Li Y et al (2012) Impacts of lead/zinc mining and smelting on the environment and human health in China. Environ Monit Assess 184(4):2261–2273. doi:10.1007/s10661-011-2115-6
Kim J, Oh JM (2015) Tissue distribution of heavy metals in heron and egret chicks from pyeongtaek, Korea. Arch Environ Contam Toxicol 68(2):283–291. doi:10.1007/s00244-014-0110-y
Mateo R, Toledo RD (2009) Lead poisoning in wild birds in Europe and the regulations adopted by different countries. In: Watson RT, Fuller M, Pokras M, Hunt WG (eds) Ingestion of lead from spent ammunition: implications for wildlife and humans. The Peregrine Fund, Boise, Idaho, USA. doi:10.4080/ilsa.2009.0107
Liu CM, Ma JQ, Sun YZ (2012) Puerarin protects rat kidney from lead-induced apoptosis by modulating the PI3K/Akt/eNOS pathway. Toxicol Appl Pharmacol 258(3):330–342. doi:10.1016/j.taap.2011.11.015
Jin X, Xu Z, Zhao X et al (2017) The antagonistic effect of selenium on lead-induced apoptosis via mitochondrial dynamics pathway in the chicken kidney. Chemosphere 180:259–266. doi:10.1016/j.chemosphere.2017.03.130
Hiraga T, Ohyama K, Hashigaya A et al (2008) Lead exposure induces pycnosis and enucleation of peripheral erythrocytes in the domestic fowl. Vet J 178(1):109–114. doi:10.1016/j.tvjl.2007.06.023
Wang L, Wang H, Li J et al (2011) Simultaneous effects of lead and cadmium on primary cultures of rat proximal tubular cells: interaction of apoptosis and oxidative stress. Arch Environ Contam Toxicol 61(3):500–511. doi:10.1007/s00244-011-9644-4
Wang H, Wang ZK, Jiao P et al (2015) Redistribution of subcellular calcium and its effect on apoptosis in primary cultures of rat proximal tubular cells exposed to lead. Toxicology 333:137–146. doi:10.1016/j.tox.2015.04.015
Gotoh T, Mori M (2006) Nitric oxide and endoplasmic reticulum stress. Arterioscler Thromb Vasc Biol 26(7):1439–1446. doi:10.1161/01.ATV.0000223900.67024.15
Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11(4):381–389. doi:10.1038/sj.cdd.4401373
Breckenridge DG, Germain M, Mathai JP et al (2003) Regulation of apoptosis by endoplasmic reticulum pathways. Oncogene 22(53):8608–8618. doi:10.1038/sj.onc.1207108
Chung HT, Pae HO, Choi BM et al (2001) Nitric oxide as a bioregulator of apoptosis. Biochem Biophys Res Commun 282(5):1075–1079. doi:10.1006/bbrc.2001.4670
Wang H, Li S, Teng X (2016) The antagonistic effect of selenium on lead-induced inflammatory factors and heat shock proteins mRNA expression in chicken livers. Biol Trace Elem Res 171(2):1–8. doi:10.1007/s12011-015-0532-z
Xing M, Zhao P, Guo G et al (2015) Inflammatory factor alterations in the gastrointestinal tract of cocks overexposed to arsenic trioxide. Biol Trace Elem Res 167(2):288–299. doi:10.1007/s12011-015-0305-8
Zhang Y, Sun L, Ye L et al (2008) Lead-induced stress response in endoplasmic reticulum of astrocytes in CNS. Toxicol Mech Methods 18(9):751–757. doi:10.1080/15376510802390908
Liu CM, Zheng YL, Lu J et al (2010) Quercetin protects rat liver against lead-induced oxidative stress and apoptosis. Environ Toxicol Pharmacol 29(2):158–166. doi:10.1016/j.etap.2009.12.006
Liu C, Sun Z, Xu Z et al. (2017) Down-regulation of microRNA-155 promotes selenium deficiency-induced apoptosis by tumor necrosis factor receptor superfamily member 1B in the broiler spleen. Oncotarget. Accepted 22 March 2017
Yao HD, Wu Q, Zhang ZW et al (2013a) Gene expression of endoplasmic reticulum resident selenoproteins correlates with apoptosis in various muscles of se-deficient chicks. J Nutr 143(5):613–619. doi:10.3945/jn.112.172395
Yao HD, Wu Q, Zhang ZW et al (2013b) Selenoprotein W serves as an antioxidant in chicken myoblasts. Biochim Biophys Acta 1830(4):3112–3120. doi:10.1016/j.bbagen.2013.01.007
Frisk P, Wester K, Yaqob A et al (2003) Selenium protection against mercury-induced apoptosis and growth inhibition in cultured K-562 cells. Biol Trace Elem Res 92(2):105–114. doi:10.1385/BTER:92:2:105
Li YF, Dong Z, Chen C et al (2012) Organic selenium supplementation increases mercury excretion and decreases oxidative damage in long-term mercury-exposed residents from Wanshan, China. Environ Sci Technol 46(20):11313–11318. doi:10.1021/es302241v
Zhang R, Yi R, Bi Y et al (2017) The effect of selenium on the Cd-induced apoptosis via no-mediated mitochondrial apoptosis pathway in chicken liver. Biol Trace Elem Res:1–10. doi:10.1007/s12011-016-0925-7
Jiao X, Yang K, An Y et al (2017) Alleviation of lead-induced oxidative stress and immune damage by selenium in chicken bursa of Fabricius. Environ Sci Pollut Res Int 24(8):7555–7564. doi:10.1007/s11356-016-8329-y
Li X, Xing M, Chen M et al (2017) Eects of selenium-lead interaction on the gene expression of inflammatory factors and selenoproteins in chicken neutrophils. Ecotox Environ Safe 139:447–453. doi:10.1016/j.ecoenv.2017.02.017
Liu L, Yang B, Cheng Y et al (2015) Ameliorative effects of selenium on cadmium-induced oxidative stress and endoplasmic reticulum stress in the chicken kidney. Biol Trace Elem Res 167(2):1–12. doi:10.1007/s12011-015-0314-7
Chen J, Pan T, Na W et al (2017) Cadmium-induced endoplasmic reticulum stress in chicken neutrophils is alleviated by selenium. J Inorg Biochem 170:169–177. doi:10.1016/j.jinorgbio.2017.02.022
Klaassen CD, Amdur MO (2007) Casarett and Doull’s toxicology: the basic science of poisons. McGraw-Hill Professional/Jaypee Brothers Medical Publishers, New York
Vengris VE, Maré CJ (1974) Lead poisoning in chickens and the effect of lead on interferon and antibody production. Can J Comp Med 38(3):328–325
Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29(9):e45. doi:10.1093/nar/29.9.e45
Komosa A, Kitowski I, Chibowski S et al (2009) Selected radionuclides and heavy metals in skeletons of birds of prey from eastern Poland. J Radioanal Nucl Ch 281(3):467–478. doi:10.1007/s10967-009-0029-3
Liu G, Wang ZK, Wang ZY et al (2016) Mitochondrial permeability transition and its regulatory components are implicated in apoptosis of primary cultures of rat proximal tubular cells exposed to lead. Arch Toxicol 90(5):1193–1209. doi:10.1007/s00204-015-1547-0
Tabas I, Ron D (2011) Integrating the mechanisms of apoptosis induced by endoplasmic reticulum stress. Nat Cell Bio 13(3):184–190. doi:10.1038/ncb0311-184
Xu W, Liu L, Charles IG et al (2004) Nitric oxide induces coupling of mitochondrial signalling with the endoplasmic reticulum stress response. Nat Cell Biol 6(11):1129–1134. doi:10.1038/ncb1188
Aktan F (2004) iNOS-mediated nitric oxide production and its regulation. Life Sci 75(6):639–653. doi:10.1016/j.lfs.2003.10.042
Zhu G, Lee AS (2015) Role of the unfolded protein response, GRP78 and GRP94 in organ homeostasis. J Cell Physiol 230(7):1413–1420. doi:10.1002/jcp.24923
Shiraishi H, Okamoto H, Yoshimura A et al (2006) ER stress-induced apoptosis and caspase-12 activation occurs downstream of mitochondrial apoptosis involving APAF-1. J Cell Sci 119(19):3958–3966. doi:10.1242/jcs.03160
Shen J, Chen X, Hendershot L et al (2002) ER stress regulation of ATF6 localization by dissociation of BiP/GRP78 binding and unmasking of Golgi localization signals. Dev Cell 3(1):99–111. doi:10.1016/S1534-5807(02)00203-4
Luo S, Baumeister P, Yang S et al (2003) Induction of Grp78/BiP by translational block: activation of the Grp78 promoter by ATF4 through and upstream ATF/CRE site independent of the endoplasmic reticulum stress elements. JBC 2003 278(39):37375–37385. doi:10.1074/jbc.M303619200
Imaizumi K, Miyoshi K, Katayama T et al (2001) The unfolded protein response and Alzheimer’s disease. Biochim Biophys Acta 1536(2–3):85–96. doi:10.1016/S0925-4439(01)00049-7
Hitomi J, Katayama T, Taniguchi M et al (2004) Apoptosis induced by endoplasmic reticulum stress depends on activation of caspase-3 via caspase-12. Neurosci Lett 357(2):127–130. doi:10.1016/j.neulet.2003.12.080
Hetz CA (2007) ER stress signaling and the BCL-2 family of proteins: from adaptation to irreversible cellular damage. Antioxid Redox Signal 9(12):2345–2355. doi:10.1089/ars.2007.1793
Tamatani M, Ogawa S, Niitsu Y et al (1998) Involvement of Bcl-2 family and caspase-3-like protease in NO-mediated neuronal apoptosis. J Neurochem 71(4):1588–1596. doi:10.1046/j.1471-4159.1998.71041588.x
Shinkai Y, Yamamoto C, Kaji T (2010) Lead induces the expression of endoplasmic reticulum chaperones GRP78 and GRP94 in vascular endothelial cells via the JNK-AP-1 pathway. Toxicol Sci 114(2):378–386. doi:10.1093/toxsci/kfq008
Shao CC, Li N, Zhang ZW et al (2014) Cadmium supplement triggers endoplasmic reticulum stress response and cytotoxicity in primary chicken hepatocytes. Ecotoxicol Environ Saf 106:109–114. doi:10.1016/j.ecoenv.2014.04.033
Tang CH, Chiu YC, Huang CF et al (2009) Arsenic induces cell apoptosis in cultured osteoblasts through endoplasmic reticulum stress. Toxicol Appl Pharmacol 241(2):173–181. doi:10.1016/j.taap.2009.08.011
Baranowska-Bosiacka I, Strużyńska L, Gutowska I et al (2013) Perinatal exposure to lead induces morphological, ultrastructural and molecular alterations in the hippocampus. Toxicology 303(1):187–200. doi:10.1016/j.tox.2012.10.027
Wang Y, Wang K, Huang H et al (2017) Alleviative effect of selenium on inflammatory damage caused by lead via inhibiting inflammatory factors and heat shock proteins in chicken testes. Environ Sci Pollut Res Int 2017:1–9. doi:10.1007/s11356-017-8785-z
Acknowledgments
All authors have read the manuscript and agreed to submit it in its current form for consideration for publication in Biological Trace Element Research. This paper has not been published or accepted for publication. It is not under consideration at another journal.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
All procedures used in this experiment were approved by the Northeast Agricultural University’s Institutional Animal Care and Use Committee under the approved protocol number SRM-06.
Funding
The study was funded by the Agricultural Science and Technology Innovation Program (ASTIPIAS07), Heilongjiang Province on Natural Fund Project (No. C201420), and Heilongjiang excellent livestock training program.
Conflict of Interest
The authors declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Wang, X., An, Y., Jiao, W. et al. Selenium Protects against Lead-induced Apoptosis via Endoplasmic Reticulum Stress in Chicken Kidneys. Biol Trace Elem Res 182, 354–363 (2018). https://doi.org/10.1007/s12011-017-1097-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12011-017-1097-9