Abstract
Insulin is involved in a number of cellular functions, including the stimulation of cell growth, cell cycle progression and glucose uptake and is a common protein supplement in serum-free mammalian cell culture media. However, several trace metals have previously been reported to exhibit insulin-like effects on specific cell types. As a step towards developing chemically-defined, protein-free media for mammalian cells, we tested the effectiveness of five trace metals (cadmium, nickel, lithium, vanadium and zinc) as a replacement for insulin. Four cell lines of biotechnological relevance were used, including the hybridoma CRL1606, the myeloma NS0, and the Chinese hamster ovary cell lines CHO-IFN and CHO-K1. Zinc was found to be an effective insulin replacement for the hybridoma, myeloma and CHO-K1 cells. Cell growth, cell cycle progression and antibody production was not affected by the substitution. Furthermore, no adaptation procedure was required.
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R.R. Balcarcel G. Stephanopoulos (2001) ArticleTitleRapamycin reduces hybridoma cell death and enhances monoclonal antibody production Biotechnol. Bioeng. 76 1–10 Occurrence Handle10.1002/bit.1020 Occurrence Handle11400101
D. Barnes G. Sato (1980) ArticleTitleMethods for growth of cultured cells in serum-free medium Anal. Biochem. 102 255–270 Occurrence Handle10.1016/0003-2697(80)90151-7 Occurrence Handle6999941
J.D. Chung A.J. Sinskey G. Stephanopoulos (1998) ArticleTitleGrowth factor and Bcl-2 mediated survival during abortive proliferation of hybridoma cell line Biotechnol. Bioeng. 57 164–171 Occurrence Handle10.1002/(SICI)1097-0290(19980120)57:2<164::AID-BIT5>3.0.CO;2-L Occurrence Handle10099191
O. Ezaki (1989) ArticleTitleIIb group metal ions (Zn2+Cd2+Hg2+) stimulate glucose transport activity by post-insulin receptor kinase mechanism in rat adipocytes J. Biol. Chem. 264 16118–16122 Occurrence Handle2550432
B.D. Follstad D.I.C Wang G. Stephanopoulos (2002) ArticleTitleMitochondrial membrane potential selects hybridomas yielding high viability in fed-batch cultures Biotechnol. Prog. 18 1–5 Occurrence Handle10.1021/bp010132b Occurrence Handle11822893
D.W. Jayme S.R. Smith (2000) ArticleTitleMedia formulation options and manufacturing process controls to safeguard against introduction of animal origin contaminants in animal cell culture Cytotechnology 33 27–36 Occurrence Handle10.1023/A:1008133717035
E.D. Saggerson S.R. Sooranna C.J. Evans (1976) ArticleTitleInsulin-like actions of nickel and other transition-metal ions in rat fat-cells Biochem. J. 154 349–357 Occurrence Handle938454
A.R. Saltiel C.R. Kahn (2001) ArticleTitleInsulin signalling and the regulation of glucose and lipid metabolism Nature 414 799–806 Occurrence Handle11742412
A. Sanfeliu J.D. Chung G. Stephanopoulos (2000) ArticleTitleEffect of insulin stimulation on the proliferation and death of Chinese hamster ovary cells Biotechnol. Bioeng. 70 421–427 Occurrence Handle10.1002/1097-0290(20001120)70:4<421::AID-BIT7>3.0.CO;2-S Occurrence Handle11005924
P.W. Sauer J.E. Burky M.C. Wesson H.D. Sternard L. Qu (2000) ArticleTitleA high-yielding, generic fed-batch cell culture process for production of recombinant antibodies Biotechnol. Bioeng. 67 585–597 Occurrence Handle10.1002/(SICI)1097-0290(20000305)67:5<585::AID-BIT9>3.3.CO;2-8 Occurrence Handle10649233
R.C. Schoen K.L. Bentley R.J. Klebe (1982) ArticleTitleMonoclonal antibody against human fibronectin which inhibits cell attachment Hybridoma 1 99–108 Occurrence Handle6208125
P. Srivastava A.K. Saxena R.K. Kale N.Z. Baquer (1993) ArticleTitleInsulin like effects of lithium and vanadate on the altered antioxidant status of diabetic rats Res. Commun. Chem. Pathol. Pharmacol. 80 283–293 Occurrence Handle8351410
X.H. Tang N.F. Shay (2001) ArticleTitleZinc has an insulin-like effect on glucose transport mediated by phosphoinositol-3-kinase and Akt in 3T3-L1 fibroblasts and adipocytes J. Nutr. 131 1414–1420 Occurrence Handle11340092
K.H. Thompson J.H. McNeill C. Orvig (1999) ArticleTitleVanadium compounds as insulin mimics Chem. Rev. 99 2561–2571 Occurrence Handle10.1021/cr980427c Occurrence Handle11749492
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Wong, V.V.T., Ho, K.W. & Yap, M.G.S. Evaluation of insulin-mimetic trace metals as insulin replacements in mammalian cell cultures. Cytotechnology 45, 107–115 (2004). https://doi.org/10.1007/s10616-004-6173-2
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DOI: https://doi.org/10.1007/s10616-004-6173-2