Keywords

ABA:

Abscisic acid

AD:

Alzheimer’s disease

AHPND:

Acute hepatopancreatic necrosis disease

ALS:

Amyotrophic lateral sclerosis

aMCI:

Amnestic mild cognitive impairment

AR:

Amalaki Rasayana

Cd:

Cadmium

Clp:

Caseinolytic protease

COMT1:

Caffeic acid O-methyltransferase1

Cpn:

Chaperonin

DBMIB:

2,5-dibromo-3-methyl-6-isopropyl-p-benzoquinone

ER:

Endoplasmic reticulum

GolS:

Galactinol synthase

GPx:

Glutathione peroxidise

H2O2 :

Hydrogen peroxide

HD:

Huntington’s disease

HSC:

Heat shock cognate

HSE:

Heat shock elements

HSF:

Heat shock factors

HSP:

Heat shock proteins

HspA:

Heat shock protein family A

HspB:

Heat shock protein family B

MG:

Methylglyoxal

miRNA:

MicroRNA

MPK3:

Mitogen-activated protein kinase

mRNA:

Messenger RNA

NLHS:

Non-lethal heat shock

NO:

Nitric oxide

Nrf2:

Nuclear factor (erythroid-derived 2)-like 2

PARK7:

Parkinson disease protein 7

PD:

Parkinson’s disease

PEG:

Polyethylene glycol

PSII:

Photosystem II

RCS:

Reactive carbonyl species

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

Se:

Selenium

sHsp:

Small heat shock proteins

SOD:

Superoxide dismutase

T2DM:

Type 2 diabetes mellitus

UPR:

Unfolded protein response

1 Introduction

Since the dawn of cellular life, all living organism in this world is constantly challenged by ever changing variables of the environment. The ability of the organism to successfully adapt to its changing environment is critical to its survival and likely represents an integral driving force in evolution. To cope up with different conditions of stress, organisms have been found to exhibit selective upregulation in the expression of a group of proteins called the heat shock proteins (Hsp). Hsp constitutes a large family of proteins that are usually classified based on their molecular weight: Hsp10, Hsp40, Hsp60, Hsp70, Hsp90, etc. Hsp have been reported to be involved in antigen presentation as chaperones in course of transfer of antigenic peptides to the class I and class II molecules of the major histocompatibility complexes (Arrigo 1994; Li et al. 2002). A link between heat shock proteins and oxidative stress has been established in a wide array of research (Sørensen 2010). Though the exact mechanisms are yet to be elucidated, it is suggested that oxidative stress can be a principal determinant of thermal tolerance (Abele et al. 2001; Pörtner 2001). The following chapter will inspect the role of heat shock proteins in oxidative stress and stress tolerance (especially thermal tolerance).

1.1 Heat Shock Proteins: An Overview

Heat shock proteins are ubiquitous proteins which render universal protective mechanisms from prokaryotes to eukaryotes to sustain cellular function and homeostasis (Table 6.1) (Lindquist and Craig 1988). These proteins were first discovered in Drosophila (Ritossa 1964) where it was found that increase in temperature of a few degrees above the physiological range induced the synthesis of these proteins from their salivary glands. The term “heat shock protein” is a misnomer. This family of proteins was originally named due to their expression after heat exposure. But now it is evident that Hsp synthesis is not only due to hyperthermia but also triggered by a wide range of environmental as well as metabolic stress conditions like heavy metal ions, ethanol, nicotine, anoxia, ischemia, glucose deprivation, surgical stress and viral agents (Feige et al. 2013; Santoro 2000). Consequently, the term ‘stress protein’ is preferably used (Whitley et al. 1999). Stress proteins belong to a multigene family and their nomenclature is given based on their molecular size (8-150 kDa). For example, Hsp 60, Hsp 70, Hsp 90 refers the family of heat shock proteins on the order of molecular size 60, 70 and 90 kDa respectively. Hsp are highly conserved and abundant in nearly all subcellular compartments. Many of these proteins show constitutive expression whereas expression level of others get increased under stressed condition (Fig. 6.1). In eukaryotic cells, heat shock factors (HSF) act as transcriptional activators for heat shock genes. There are different families of HSF that get activated under several stressed conditions. Among them, HSFs 1 and 3 function as stress responsive activators and show maximal heat shock responsiveness (Tanabe et al. 1998), whereas HSF 2 is activated during embryonic development and differentiation (Schuetz et al. 1991; Sistonen et al. 1992). HSF 4 seems to be preferentially expressed in the human heart, brain, skeletal muscle and pancreas (Nakai et al. 1997). HSF recognizes modular sequence elements referred to as HSE (a series of pentameric units arranged as inverted adjacent arrays of the sequence 5′-nGAAn-3′) located within the promoter region of heat shock gene (Amin et al. 1988; Perisic et al. 1989). In inactive stage, heat shock factors exist in monomeric form. But when activated, they trimerize into an active form that is capable of binding to the heat shock element (HSE) site of the stress protein gene and initiating transcription and translation of heat shock protein.

Table 6.1 Cellular location and function of mammalian heat shock proteins
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Fig. 6.1
figure 1

Role of heat shock proteins in various conditions of stress

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Stress proteins function as intracellular chaperones that permit the maturation and correct folding of most of the proteome. They play a crucial role in three dimensional folding of the newly translated polypeptide chain and assist to form proper protein conformation. In fact, they ensure that the newly synthesized polypeptide chain proceed correctly through successive folding and unfolding mechanism to achieve their functional conformation. They can recognize non-native conformation of the polypeptide and prevent their aggregation by binding to hydrophobic residues that have been exposed during translocation or stress induced damage (Pirkkala and Sistonen 2001). Upon exposure of extreme stress condition, the damaged protein loses its ability to be successfully refolded. Hsp promote ubiquitin mediated proteasomal degradation of these abnormal, unstable proteins. Furthermore, they mediate protein translocation across organellar membranes. It has been found that synthesis of these stress proteins under non-lethal temperature appears to protect the organism from upcoming high temperature or other stress that would be otherwise lethal. In the case of exposure to heat, this phenomenon has been called ‘thermotolerance’. Clinical evidences suggest that stress protein synthesis under hyperthermic condition may provide potential safeguard against cardiac ischemia, arterial injury, endotoxic shock, renal and hepatic ischemia, ethanol-induced gastric ulcerations and skeletal muscle ischemia-reperfusion (Morimoto and Santoro 1998; Suzuki et al. 1997). Stress proteins play a pivotal role in the maintenance of cellular homeostasis by regulating immunity, cell cycle progression and apoptosis during development and differentiation. HSP have a significant role on adaptive immunity. During the time of antigen presentation, these molecular chaperons (HSP) associate with a wide range of antigenic peptides and facilitate the delivery of antigenic peptides to the class I and class II molecules of the major histocompatibility complexes. In addition, extracellular HSP can stimulate professional antigen presenting cells (macrophages, dendritic cells) to onset immune response (Li et al. 2002). Members of Hsp family especially Hsp 27 and Hsp 70 function as potent antiapoptotic molecules. Upon exposure to oxidative stress, Hsp 27 inhibits cytochrome c release where inducible Hsp70 prevents apoptosis by interfering with the signaling cascades and by impairing the activation of effector caspases (Pirkkala and Sistonen 2001).

1.2 Role of Heat Shock Proteins in Oxidative Stress

Heat stress activates HSFs and also lead to accumulation of reactive oxygen species (ROS), thereby inducing oxidative damage. The HSFs bind to the HSE of the promoter region of HSF, Hsp, ROS scavenging genes and miRNA 398. miRNA 398 downregulates SOD scavengers, thereby leading to rapid accumulation of ROS. This activates Hsp which in turn, activates the ROS scavengers to avoid cellular damage (Fig. 6.2) (Driedonks et al. 2015). A range of physiological stimuli (oxidative stress, hypothermia, hyperthermia, ischemia-reperfusion, hypoxia, acidosis etc.) activate HSFs, which then get separated from HSP. On phosphorylation by protein kinases, HSFs form trimers in the cytosol. The trimer complexes then enter the nucleus and bind to the HSE in the promoter region of the corresponding Hsp gene. Hsp mRNA gets transcribed and leaves the nucleus for the cytosol. Hsp usually function as molecular chaperones and assist in the assembly and translocation of newly synthesized proteins within the cell along with the repair and refolding of damaged proteins (Kregel 2002). Constitutively expressed housekeeping molecular chaperones maintain cellular redox status and integrity of mitochondria (cytosolic Hsp), protect and facilitate the assembly of respiratory complexes and facilitate their assembly (mitochondrial Hsp) (Kuzmin et al. 2004).

Fig. 6.2
figure 2

Mechanism of action of heat sock proteins

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Selenium (Se), a dietary trace element exhibits antioxidant properties. Recent experiments on chicken liver have shown that Hsp play an important role in the oxidative stress induced damage during Se deficiency. It has been reported that expression of Hsp 27, 40, 60, 70, and 90 increase with increment in oxidative stress during Se deficiency. Hsp have been found to exert protective effects during the generation of oxidative stress due to Se deficiency (Liu et al. 2015). Studies have shown that accumulation of ROS in yeast (Saccharomyces cerevisiae) is associated with the induction of a heat shock reporter gene over a range of heat shock temperatures (33-44°C). ROS-mediated signaling ensures cooperation between heat shock and antioxidant responses (Moraitis and Curran 2004).

Hsp 70 protects cells from oxidative damage. They bind to stress exposed hydrophobic residues of denatured proteins, thereby preventing them from aggregating and promoting refolding. In the thermophile anaerobe (Thermatoga maritima), Hsp 70 exhibits redox sensitive binding to concerned peptides in response to oxidative stress. It interacts with an E3 ubiquitin ligase to transfer proteins towards proteolysis (Lüders et al. 2000; Rajkumar et al. 2015).

Most neurons contain high levels of Hsc70 and low levels of Hsp70 (Cruz et al. 1991). In motor neurons, both forms of Hsp are present, but no increase in endogenous expression is observed during heat shock. Extracellular Hsp70 inhibits apoptosis. Johnson et al. (Johnson et al. 1990; Johnson et al. 1995) have shown that Hsc/Hsp70 improves resistance to nutrient-deprivation stress when bound to arterial smooth muscle cells after being added to the culture medium in vitro. Similar observations have been found in case of cultured monocytes (Guzhova et al. 1998). Tidwell et al. have shown that in vivo administration of a mixture of Hsc/Hsp70 inhibits motor and sensory neuronal degeneration after sciatic nerve axotomy (Tidwell et al. 2004; Yu et al. 2001). Oxidative stress is characteristic of different protein misfolding associated diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD) and Amyotrophic lateral sclerosis (ALS) (Andersen 2004; Rauchova et al. 2012; Yu et al. 2001). Oxidative stress disturbs calcium homeostasis, mitochondrial and cytoskeletal functions and can induce neuronal cell death. Thus, apoptosis have been reported in different neurodegenerative diseases (Friedlander 2003; Mattson 2000; Wyttenbach and Arrigo 2009). rhHsp70 protects motor neurons subjected to oxidative stress, common in neurodegenerative diseases such as AD, PD, ALS etc. (Robinson et al. 2005). The levels of different Hsp have been reported to increase in the brain of neurodegenerative disease patients (Brownell et al. 2012; Sun and MacRae 2005; Tóth et al. 2015; Wilhelmus et al. 2006). Several members of the HSPB family have been observed in the senile plaques and cerebral amyloid angiopathy of AD patients. HSPA1 have been found to colocalize with Aβ peptides and α-synuclein. HSPA8 has been found in intracellular inclusions in ALS (Muchowski and Wacker 2005). Overexpression of members of DNAJ protein family suppress the nuclear aggregation of mutant ataxin-1 and ataxin-3 thereby decreasing their toxicity in vitro model (Chai et al. 1999; Cummings et al. 2001). Overexpression of HSPA has been found to decrease polyglutamine induced neurodegeneration in Drosophila model of polyglutamine disease (Warrick et al. 1999).

ROS generation in the brain of AD patients lead to the increased expression of HSC 71, Hsp 27, HDJ 1 etc. (Najarzadegan et al. 2016). Poly(Q) mutation can generate ROS and is therefore prevented by Hsp 27 (Wyttenbach et al. 2002). HDJ-1 preserves mitochondrial function and proteasomal activity following oxidative injury (Ding and Keller 2001). Increased level of oxidation in AD brain is induced by HSC 71 (Castegna et al. 2002). Recent observations of the mechanism of induction of HSP and the decrease in the levels of Thioredoxin 1 in amnestic mild cognitive impairment (aMCI) brain suggest that alteration in the chaperone systems may contribute to the pathogenesis and progression of AD (Di Domenico et al. 2010).

Glial cells have been speculated to supply neighboring neurons with Hsp 70 by means of motor neurons during conditions of stress (Tytell et al. 1986). On the other hand, the HSPB protect cells from apoptosis and oxidative insult by binding to the cytoskeletal proteins (Tóth et al. 2015). HSPB decrease the level of ROS and regulate intracellular redox homeostasis, thereby protecting cytoskeleton, an important target for oxidative stress (Golenhofen et al. 2006; Mymrikov et al. 2011). HSPB 5/HSPB 2 deficiency affects cardiac function pointing towards their possible role in maintaining normal cardiac functions (Golenhofen et al. 2006; Morrison et al. 2004; Ray et al. 2001).

Ethanol consumption results in increased generation of ROS (Wu and Cederbaum 2003). The protective effects of HSP against ethanol induced toxicity have been reported in case of brain and hepatic cells (Russo et al. 2001). Vogt and coworkers (2001) have reported that metabolic stress caused by the high intensity activity, rather than stimulated hypoxia, is the primary cause of activation of Hsp 70. The accumulation of lactate and alterations of pH during intensive exercise act as the primary stimuli for Hsp expression (Mc Naughton et al. 2006). The heat shock protein 70–2 (HSPA1B) and 70-hom (HSPA1L) genes and their functional polymorphisms have been reported to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM) (Umapathy et al. 2012). Toxic metals are associated with induction of oxidative stress. Accumulation of Cu2+ is associated with genetic disorders such as Wilson’s and Menke’s disease. Small Hsp (sHsp) such as Hsp27 and αB-crystallin bind to Cu2+ and inhibit Cu2+ mediated generation of ROS (Bakthisaran et al. 2015).

1.3 Role of Heat Shock Proteins in Stress Tolerance in Prokaryotes

Study of Sakthivel et al. have shown that HSPA and small heat shock proteins in general, play an important role in oxidative stress tolerance and help to stabilize membrane proteins like the photosystems and phycobilisomes in the cyanobacterium. In this study, both wild type and an hspA deleted strain from Synechocystis sp. PCC 6803 were being compared in the presence of methyl viologen or peroxide stress. The results showed that the cell growth, viability and pigment contents in thylakoid membranes were markedly reduced in the mutant even after enhancing the expression of other molecular chaperones. But Synechococcus elongatus strain ECT16–1, which constitutively expresses HSPA showed a much better cell growth and viability. The reduction of pigment contents was also arrested after 24 h in this strain (Sakthivel et al. 2009). It has been reported that Salmonella typhimurium gets adapted to oxidative stress when pre-treated with non-lethal dose of hydrogen peroxide by virtue of the induction of 30 proteins. Of these, 9 are constitutively overexpressed in hydrogen peroxide resistant oxyR mutants. Mutant oxyR1 is resistant to oxidizing agents and overexpresses 3 Hsp (D 64a, E 89, F 52a). The oxyR regulatory network is a previously uncharacterized global regulatory network in enteric bacteria (Christman et al. 1985).

1.4 Role of Heat Shock Proteins in Stress Tolerance in Plants

Heat stress induces protein denaturation which in turn, phosphorylates and activates Hsp 60, 70, 90, 100. Hsp 70 can be obtained from tomato rice etc., Hsp 90 from maize, wheat etc., Hsp 70 from Soyabean, Hsp 60 from barley, rye and sHsp from millet, sorghum etc. 7Hsp 70, Hsp 60 (Chaperonin), Hsp 90, Hsp 100/Clp and small Hsp act as molecular chaperones and impart plant tolerance to various modes of stress. The various subfamilies (DnaK, Hsp 110) of Hsp 70 are distributed in the cytosol, chloroplast, mitochondria and endoplasmic reticulum. They are associated with the prevention of protein aggregation and assistance in refolding, translocation, transcriptional activation and signal transduction. The various subfamilies (Cpn 60 etc.) of Hsp 60 are distributed in the cytosol and mitochondria and assist in protein folding. The various subfamilies (AtHsp 90–1, 5, 6, 7) of Hsp 90 are found in the cytosol, chloroplast, mitochondria and endoplasmic reticulum. They facilitate genetic buffering and signal transduction. The various subfamilies (Clp B, Clp D etc.) of Hsp 100 are found in the cytosol, chloroplast and mitochondria and assist in protein unfolding. The various subfamilies (Hsp 17.6, 17.9 etc.) of sHsp are found in the cytosol, chloroplast, mitochondria and endoplasmic reticulum. They prevent protein aggregation and stabilize non-native proteins (Usman et al. 2014).

Hsp104, Hsp70, and Hsp40 are predominant during replication. On the other hand, Hsp90 is associated with transcriptional and post-transcriptional processes. Hsp70 and Hsp90, in combination, plays a major role in morphogenesis. Heat stress in fungi lead to increased expression of Hsp10, Hsp30, Hsp60, Hsp90, and Hsp104 proteins, while expression of Hsp12 increases in response to cold stress. Osmotic stress is controlled by small heat shock proteins and Hsp60. Expression of Hsp30, Hsp70, and Hsp90 increases in response to pH stress. Hsp104 is also associated with conditions of high pressure. Recent experimentations suggest that Hsp90 can be a potential antifungal target due to its role in morphogenesis (Tiwari et al. 2015).

In another study, the expression level of a small heat shock protein EsHsp16.9, isolated from Siberian wild rye (Elymus sibiricus) increases when exposed to stressors like heat, drought, arsenic, methyl viologen and H2O2 treatment. In vitro study, this protein has reduced thermal aggregation of malate dehydrogenase. When this EsHsp16.9 is expressed in E. coli, it shows better cell growth under salt, arsenic, polyethylene glycol and heat (Lee et al. 2015). The yeast metallothionein gene CUP1 is transcriptionally activated during oxidative stress by means of a functional HSE and HSF. CUP1 imparts metal detoxification and protects against oxidative insult (Liu and Thiele 1996).

Heat stress is a primary factor of deterioration in summer creeping bentgrass (Agrostis stolonifera) (Heat Shock Proteins in Relation to Heat Stress Tolerance of Creeping Bentgrass at different nitrogen levels). Nitrogen medium helped the grass to better survive during long term heat stress. Fv/Fm, a correlation between chloroplast-sHsp production and PSII efficiency indicates that this chloroplast-sHsp plays a direct role in the protection of PSII (Heckathorn et al. 1998). 38It is also reported that heterologous expression of MsHsp 23in creeping bentgrass protects against thermal stress by chaperone activity, associated with the induction of ascorbate peroxidase.

Now-a-days, cross-stress tolerance possesses an important role in producing stress-resistant crops. Heat or cold priming-induced cross-tolerance is very common in plants. Multiple stress signaling pathways involving ROS, RNS, reactive carbonyl species (RCS), most particularly H2O2, nitric oxide (NO) and methylglyoxal (MG) provide resistance to abiotic stresses via modulating the expression of genes as well as modifying proteins post-translationally (Hossain et al. 2017). ROS influences the stress tolerance in the yeast. H2O2 promotes accumulation of Hsp 70 and Hsp 90 mRNA (Moraitis and Curran 2004). ROS, H2O2, and 2, 5-dibromo-3-methyl-6-isopropyl-p-benzoquinone (DBMIB), an endogenous H2O2 propagator induces HsfA3 transcription in seedlings leading to oxidative stress tolerance. The overexpression of several genes encoding galactinol synthase (GolS) increase galactinol levels (Song et al. 2016).

Studies in Arabidopsis (Arabidopsis thaliana) have shown that induction of HSFA4A enhances tolerance to salt and oxidative agents via altering transcription of a large set of genes. Its inactivation results in hypersensitivity to salt stress. hsfa4a mutants elevate H2O2 accumulation and lipid peroxidation (Pérez-Salamó et al. 2014). Chaperone production and improvement of stress resistance in arabidopsis can be elevated by overexpressing AtHSFA1b, AtHSFA2, AtHSFA3, AtHsfA4a and AtHSFA6a (Jacob et al. 2016) but this may lead to moderate to severe dwarfism (Yoshida et al. 2011). Alfalfa, (Medicago sativa) overexpressing Hsp gene (MsHSP70) is less sensitive to polyethylene glycol (PEG) than control group (Li et al. 2017). Arabidopsis Hsp 21 is a crucial component of thermomemory. It is a plastidial small heat shock protein that rapidly accumulates after heat stress (Sedaghatmehr et al. 2016). Lack of functional FtsH6, a plastid-localized metalloprotease promotes Hsp 21 accumulation during the later stages of thermomemory and increases thermomemory capacity.

In yeast (Saccharomyces cerevisiae) two-hybrid and bimolecular fluorescence complementation assays, homomeric interaction of HSFA4A is reduced by alanine replacement of three conserved cysteine residues. MPK3 and MPK6 phosphorylate HSFA4A in vitro on three distinct sites, among them serine-309 is the major phosphorylation site. They can form in vivo complexes with ZAT10/salt tolerance zinc finger and thus regulate plant defense responses (Mittler et al. 2006; Nguyen et al. 2012).

CsHSP17.2, a molecular chaperone present in the cytosol and the nucleus is essential for thermotolerance by maintaining maximum photochemical efficiency and protein synthesis, enhancing the scavenging ROS and inducing the expression of HS-responsive genes in tea plants (Camellia sinensis) (Wang et al. 2017). Its expression is significantly upregulated by heat stress. Transgenic E. coli and Pichia pastoris expressing CsHSP17.2 exhibit enhanced thermotolerance.

DcHsp17.7, another cytosolic Class I heat shock protein accumulates in carrot (Daucus carota) leaf tissue under oxidative and osmotic (PEG) stress conditions (Ahn and Song 2012). Heterologously expressed DcHsp17.7 enhanced E. coli cell viability under various abiotic stress conditions such as salinity (Song and Ahn 2011), heat (Kim and Ahn 2009), cold (Song and Ahn 2010), oxidation and osmotic stress. Transgenic carrot plants overexpressing DcHsp17.7 showed higher thermotolerance (Malik et al. 1999) and transgenic potato plants showed enhanced cellular membrane stability and tuberization under heat stress (Ahn et al. 2004).

Genetic engineering develops crop plants possessing enhanced stress tolerance (Bhatnagar-Mathur et al. 2008). During abiotic stress, methylglyoxal accumulates to toxic levels in affected cells. In stress affected cells it is routinely detoxified through the action of DJ1/PARK7/Hsp31 proteins via targeting mitochondria and inducing expression of key stress-related genes. Hsp31 confers dual biotic and abiotic stress tolerance inNicotiana tabacum as well as stress tolerance against diverse biotic stress inducers such as viruses, bacteria and fungi in tobacco plants (Melvin et al. 2017). 39On the other hand, the Hsp 90 and isocitrate lyase genes of Nicotiana tobacum plants have been reported to be associated with the development and reproduction of a root knot nematode Meloidogyne incognita.

HSFA6b plays a pivotal role in the response to ABA and in thermotolerance (Huang et al. 2016). ABA-responsive element-binding protein1 activates the HSFA6B promoter, as a result increased HSFA6B directly binds to the promoter of dehydration-responsive element-binding protein2A and enhances its expression. Under salt stress conditions, ER-sHsp transgenic plants have more vigorous roots, maintain a higher relative water content, absorb less sodium, accumulate more osmolytes, and sustain less damage to the photosystem, compared to wild-type non-transgenic plants. This study proves that UPR signaling pathway affects plant abiotic tolerance (Fu et al. 2016).

The tomato (Lycopersicon esculentum) chloroplast small heat shock protein (sHsp), Hsp 21 is induced by thermal stress in leaves and in developing fruits in course of transition of chloroplasts to chromoplasts. Hsp 21 protects PSII from temperature dependent oxidative stress. Analysis of leaf phenotype, chlorophyll content, and photosynthetic efficiency reveals that silencing of heat-shock factor A1a (HsfA1a) gene decreases melatonin levels and cadmium (Cd) tolerance, whereas its overexpression enhances the expression of the melatonin biosynthetic gene caffeic acid O-methyltransferase1 (COMT1) and melatonin accumulation leading to Cd tolerance in tomato plants (Cai et al. 2017; Neta-Sharir et al. 2005).

1.5 Role of Heat Shock Proteins in Stress Tolerance in Animals

A study by Dwivedi and Lakhotia have shown that Amalaki Rasayana (AR), an ayurvedic herbal formulation, improves tolerance in Drosophila melanogaster against crowding, thermal (Dwivedi et al. 2012; Wang et al. 2004) or oxidative stress. The expression of Hsp 27 which is important in stress tolerance like starvation, oxidative stress and in life span determination (Hao et al. 2007; Pandey et al. 2016; Shi et al. 2011; Wang et al. 2004) is elevated in both AR-fed wild type control and AR-treated heat shocked larvae (Dwivedi and Lakhotia 2016).

Antarctic sea urchin (Sterechinus neumayeri) are reported to be capable of overexpressing stress proteins (Hsp 90, Hsc 70, Hyou 1etc.) as a result of thermal stress (González et al. 2016).

It is reported that Hsp 70 family of proteins are essential for the cellular survival from heat stress and other types of physiological challenges in fish. Although programs of gene therapy have made impressive advances in recent years, the over expression of Hsp70 has proven to be problematic. Thus, its therapeutic role needs further investigation (Basu et al. 2002).

However, it has been shown that oxidative stress mediates upregulation of Hsp 90α in the hepatocytes of Mugil cephalus living in a polluted estuary. The stress resistance imparted by Hsp 90α involves proteins such as apoptosis signal-regulating kinase 1 (ASK 1), c-Jun NH2-terminal protein kinase 1/2, signal transducers and activators of transcription (STAT), extracellular signal-regulated kinase 1/2 (ERK 1/2), protein kinase B, nuclear factor-kappa B (NF kB), Ets-like protein 1, and B cell lymphoma-2 (Padmini and Rani 2011).

According to one study, both acute and chronic non-lethal heat shock (NLHS) treatment enhances the survival rate of shrimps Peneaus vannamei against acute hepatopancreatic necrosis disease (AHPND) caused by Vibrio parahaemolyticus than non-treated shrimps (Junprung et al. 2017). The authors have shown that the expression levels of heat shock proteins like LvHSP70, LvHSP90 and immune-related genes like LvproPO and LvCrustin are upregulated in chronic NLHS treated shrimps. But in shrimps with LvHSP70 and LvHSP90 gene knockdown, tolerance against chronic NLHS was absent, suggesting a vital role of heat shock proteins like Hsp70 and Hsp90 in bacterial defence in shrimp. Not only that, knockdown of Hsp 70 also influences the heat and bacterial infection tolerance in Artemia franciscana nauplii (Iryani et al. 2017). Fishes of hot spring run-off areas (Puntius sophore) have shown high expression level of Hsp 90 and Hsp 47 to tolerate heat shock (Mahanty et al. 2017).

Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) helps in stress tolerance. A study by Mohanty et al. have shown that dietary curcumin supplementation in Puntius sophore enhances the expression levels of Nrf-2, SOD, catalase, gpx, Hsp 60, Hsp 70, Hsp 90 and Hsp 110 in gill and liver compared to control group. The result suggests that curcumin supplemented group exerts better stress tolerance via Nrf2 induced upregulation of various antioxidative enzymes and heat shock proteins (Mahanty et al. 2017). According to another study, in thermal tolerance, the expression mode of Hsp 70 is much more crucial than Hsp 70 itself. When P. olivaceus and the hybrids (P.olivaceus ♀ × P. dentatus ♂) are subjected to both acute and chronic heat stress, the hybrids shows better thermotolerence via increased temperature thresholds, shorter durations, stronger magnitudes and increased delays of Hsp 70expression (Liu et al. 2017).

Kurino et al. have shown in their study that Caenorhabditis elegans exertsmore longevity and thermotolerance when treated with isoamyl alcohol and acetic acid as odor stimuli. In presence of isomethyl alcohol, the expression levels of SOD 3 and Hsp 12.6 are increased and heat stress tolerance is mediated through DAF-16 activation whereas acetic acid odor stimulus increases the expression level of Hsp 16.2 and the stress tolerance is mediated through HSF-1 activation (Kurino et al. 2017).

2 Conclusions

Owing to their evolutionary significance, heat shock proteins have been extensively studied. Their link with oxidative stress has been reported in a wide range of studies. However, their detailed molecular mechanisms are yet to be investigated. Oxidative stress has also been reported to be a principal component of thermal tolerance. This chapter has ventured into the ocean of information put forward by a wide range of research articles related to the role of heat shock proteins in oxidative stress. The related studies have imparted valuable knowledge of the interplay of heat shock proteins and oxidative insult in a wide range of diseases like Alzheimer’s, Parkinson, diabetes etc. The various mechanisms of stress tolerance associated with heat shock proteins have also been provided with respect to prokaryotes, plants and animals.