Skip to main content

Advertisement

Log in

The glutathione antioxidant system is enhanced in growth hormone transgenic coho salmon (Oncorhynchus kisutch)

  • Original Paper
  • Published:
Journal of Comparative Physiology B Aims and scope Submit manuscript

Abstract

Insertion of a growth hormone (GH) transgene in coho salmon results in accelerated growth, and increased feeding and metabolic rates. Whether other physiological systems within the fish are adjusted to this accelerated growth has not been well explored. We examined the effects of a GH transgene and feeding level on the antioxidant glutathione and its associated enzymes in various tissues of coho salmon. When transgenic and control salmon were fed to satiation, transgenic fish had increased tissue glutathione, increased hepatic glutathione reductase activity, decreased hepatic activity of the glutathione synthesis enzyme γ-glutamylcysteine synthetase, and increased intestinal activity of the glutathione catabolic enzyme γ-glutamyltranspeptidase. However, these differences were mostly abolished by ration restriction and fasting, indicating that upregulation of the glutathione antioxidant system was due to accelerated growth, and not to intrinsic effects of the transgene. Increased food intake and ability to digest potential dietary glutathione, and not increased activity of glutathione synthesis enzymes, likely contributed to the higher levels of glutathione in transgenic fish. Components of the glutathione antioxidant system are likely upregulated to combat potentially higher reactive oxygen species production from increased metabolic rates in GH transgenic salmon.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

Abbreviations

CAT:

Catalase

DTNB:

5,5′-Dithiobis(2-nitrobenzoic acid)

GCS:

γ-Glutamylcysteine synthetase

GH:

Growth hormone

GPx:

Glutathione peroxidase

GR:

Glutathione reductase

GSH:

Glutathione

GSSG:

Oxidized glutathione

γGT:

γ-Glutamyltranspeptidase

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

References

  • Altan O, Oguz I, Erbayraktar Z, Yimaz O, Bayraktarl H, Sis B (2005) The effect of prolonged fasting and refeeding on GSH-Px activity, plasma glucose and cholesterol levels and welfare of older hens from different genotypes. Archiv Geflügelkunde 69:185–191

    CAS  Google Scholar 

  • Arrigo A-P (1999) Gene expression and the thiol redox state. Free Radic Biol Med 27:936–944. PII S0891-5849(99)00175-6

  • Bartke A (1998) Growth hormone and aging. Endocrine 8:103–108. PII S0891-5849(99)00175-6

    Google Scholar 

  • Beyea JA, Olson DM, Harvey S (2005) Growth hormone (GH) action in the developing lung: changes in lung proteins after adenoviral GH overexpression. Dev Dyn 234:404–412. doi: 10.1002/dvdy.20538

    Google Scholar 

  • Brown-Borg HM, Johnson WT, Rakoczy SG, Romanick MA (2001) Mitochondrial oxidant generation and oxidative damage in Ames dwarf and GH transgenic mice. Age 24:85–100

    Article  CAS  Google Scholar 

  • Brown-Borg HM, Rakoczy SG, Romanick MA, Kennedy MA (2002) Effects of growth hormone and insulin-like growth factor-1 on hepatocyte antioxidant enzymes. Exp Biol Med 227:94–104

    CAS  Google Scholar 

  • Brown-Borg HM, Rakoczy SG (2003) Growth hormone administration to long-living dwarf mice alters multiple components of the antioxidative defense system. Mech Ageing Dev 124:1013–1024. doi: 10.1016/j.mad.2003.07.001

    Google Scholar 

  • Brown-Borg HM, Rakoczy SG, Uthus EO (2005) Growth hormone alters methionine and glutathione metabolism in Ames dwarf mice. Mech Ageing Dev 126:389–398. doi: 10.1016/j.mad.2004.09.005

    Google Scholar 

  • Carlson JC, Bharadwaj R, Bartke A (1999) Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH. Age 22:181–186

    Article  CAS  Google Scholar 

  • Cherbonnier C, Déas O, Carvalho G, Vassal G, Dürrbach A, Haeffner A, Charpentier B, Bénard J, Hirsch F (2003) Potentiation of tumor apoptosis by human growth hormone via glutathione production and decreased NF-κB activity. Br J Cancer 89:1108–1115. doi: 10.1038/sj.bjc.6601223

    Google Scholar 

  • Cook JT, McNiven MA, Sutterlin AM (2000) Metabolic rate of pre-smolt growth-enhanced transgenic Atlantic salmon (Salmo salar). Aquaculture 188:33–45. PII S0044-8486(00)00332-X

    Google Scholar 

  • Devlin R, Yesaki T, Biagi C, Donaldson E (1994) Extraordinary salmon growth. Nature 371:209-210. doi: 10.1038/371209a0

    Google Scholar 

  • Devlin RH, Johnsson JI, Smailus DE, Biagi CA, Jönsson E, Björnsson BT (1999) Increased ability to compete for food by growth hormone-transgenic coho salmon Oncorhynchus kisutch (Walbaum). Aquac Res 30:479–482

    Article  Google Scholar 

  • Devlin RH, Biagi CA, Yesaki TY (2004) Growth, viability and genetic characteristics of GH transgenic coho salmon strains. Aquaculture 236:607–632. doi: 10.1016/j.aquaculture.2004.02.026

    Google Scholar 

  • Di Simplicio P, Rossi R, Falcinelli S, Ceserani R, Formento ML (1997) Antioxidant status in various tissues of the mouse after fasting and swimming stress. Eur J Appl Physiol 76:302–307

    Article  CAS  Google Scholar 

  • Donahue AN, Aschner M, Lash LH, Syversen T, Sonntag WE (2006) Growth hormone administration to aged animals reduces disulfide glutathione levels in hippocampus. Mech Ageing Dev 127:57–63. doi: 10.1016/j.mad.2005.09.003

    Google Scholar 

  • Dziubek K (1987) Glutathione metabolism in selected organs of Rana temporaria L. in annual cycle and under different stressors. Part II. Starvation and temperature effects. Acta Biologica Cracoviensia ser. Zoologica 29:55–68

    Google Scholar 

  • Forman HF, Liu R-M (1997) Glutathione cycling in oxidative stress. In: Clerch B, Massaro DJ (eds) Oxygen, gene expression and cellular function. Dekker, New York, pp 99–121

    Google Scholar 

  • Fridovich I (2004) Mitochondria: are they the seat of senescence? Aging Cell 3:13–16. doi: 10.1111/j.1474-9728.2003.00075.x

    Google Scholar 

  • Gallagher EP, Hasspieler BM, Di Giulio RT (1992) Effects of buthionine sulfoximine and diethyl maleate on glutathione turnover in the channel catfish. Biochem Pharmacol 43:2209–2215

    Article  PubMed  CAS  Google Scholar 

  • Griffith OW (1980) Determination of glutathione and glutathione disulfide using glutathione reductase and 2-vinylpyridine. Anal Biochem 106:207–212

    Article  PubMed  CAS  Google Scholar 

  • Hauck SJ, Bartke A (2001) Free radical defenses in the liver and kidney of human growth homone transgenic mice: possible mechanisms of early mortality. J Gerontol A 56:B153–B162

    CAS  Google Scholar 

  • Hayes JD, McLellan LI (1999) Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defense against oxidative stress. Free Radic Res 31:273–300

    Article  PubMed  CAS  Google Scholar 

  • Hum S, Robitaille L, Hoffer LJ (1991) Plasma glutathione turnover in the rat: effect of fasting and buthionine sulfoximine. Can J Physiol Pharmacol 69:581–587

    PubMed  CAS  Google Scholar 

  • Kidd PM (1997) Glutathione: systemic protectant against oxidative and free radical damage. Alternat Mede Rev 2:155–176

    Google Scholar 

  • Kolątaj A, Ryińska J, Flak P (1998) The influence of selection on stress reactivity in mice. Part VI. Effect of starvation and T3 injection on the level of glutathione in liver and kidney. J Anim Breed Genet 115:407–411

    Google Scholar 

  • Leggatt RA (2006) Glutathione in fish: transport, influence of temperature and growth rate, and interactions with the stress response. Thesis (Ph.D.) University of British Colmbia, Vancouver

  • Leggatt RA, Devlin RH, Farrell AP, Randall DJ (2003) Oxygen uptake of growth hormone transgenic coho salmon during starvation and feeding. J Fish Biol 62:1053–1066. doi: 10.1046/j.1095-8649.2003.00096.x

    Google Scholar 

  • Leggatt RA, Scheer KW, Afonso LOB, Iwama GK (2006) Triploid and diploid rainbow trout do not differ in their stress response to transportation. North Am J Aquac 68:1–8. doi: 10.1577/A05-035.1

    Google Scholar 

  • Meister A (1995) Strategies for increasing cellular glutathione. In: Packer L, Cadenas E (eds) Biothiols in health and disease. Dekker, New York, pp 165–188

    Google Scholar 

  • Meister A, Tate SS, Griffith OW (1981) γ-Glutamyl transpeptidase. Meth Enzymol 77:237–253

    PubMed  CAS  Google Scholar 

  • Morales AE, Pérez-Jiménez A, Hidalgo MC, Abellán E, Cardenete G (2004) Oxidative stress and antioxidant defenses after prolonged starvation in Dentex dentex liver. Comp Biochem Physiol C 139:153–161. doi: 10.1016/j.cca.2004.10.008

    Google Scholar 

  • Muradian KK, Utko NA, Mozzhukhina TG, Litoshenko AY, Pishel IN, Bezrukov VV, Fraifield VE (2002) Pair-wise linear and 3D nonlinear relationships between the liver antioxidant enzyme activities and the rate of body oxygen consumption in mice. Free Radic Biol Med 33:1736–1739. PII S0891-5849(02)01196-6

    Google Scholar 

  • Nakano T, Sato M, Takeuchi M (1992) Partial purification and properties of glutathione peroxidase from carp hepatopancreas. Comp Biochem Physiol B 102:31–35

    Article  PubMed  CAS  Google Scholar 

  • Ogasawara T, Ohnhaus EE, Hoensch HP (1989) Glutathione and its related enzymes in the small intestinal-mucosa of rats—effects of starvation and diet. Res Exp Med 189:195–204

    Article  CAS  Google Scholar 

  • Pascual P, Pedrajas JR, Toribio F, López-Barea J, Peinado J (2003) Effect of food deprivation on oxidative stress biomarkers in fish (Sparus aurata). Chem Biol Interact 145:191–199. doi: 10.1016/S0009-2797(03)00002-4

    Google Scholar 

  • Pastore A, Federici G, Bertini E, Piemonte F (2003) Analysis of glutathione: implication in redox and detoxification. Clin Chim Acta 333:19–39. doi: 10.1016/S0009-8981(03)00200-6

    Google Scholar 

  • Raven PA, Devlin RH, Higgs DA (2006) Influence of dietary digestible energy content on growth, protein and energy utilization and body composition of growth hormone transgenic and non-transgenic coho salmon (Oncorhynchus kisutch). Aquaculture 254:730–747. doi: 10.1016/j.aquaculture.2005.11.009

    Google Scholar 

  • Rise ML, Douglas SE, Sakhrani D, Williams J, Ewart KV, Rise M, Davidson WS, Koop BF, Devlin RH (2006) Multiple microarray platforms utilized for hepatic gene expression profiling of growth hormone transgenic coho salmon with and without ration restriction. J Mol Endocrinol 37:259–282

    Article  PubMed  CAS  Google Scholar 

  • Rollo CD (2002) Growth negatively impacts the life span of mammals. Evol Dev 4:55–61

    Article  PubMed  Google Scholar 

  • Rollo CD, Carlson JC, Sawada M (1996) Accelerated aging of giant transgenic mice is associated with elevated free radical processes. Can J Zool 74:606–620

    CAS  Google Scholar 

  • Romanick MA, Rakoczy SG, Brown-Borg HM (2004) Long-lived Ames dwarf mouse exhibits increased antioxidant defense in skeletal muscle. Mech Ageing Dev 125:269–281. doi: 10.1016/j.mad.2004.02.001

    Google Scholar 

  • Seelig GF, Meister A (1985) Glutathione biosynthesis—gamma-glutamylcysteine synthetase from rat-kidney. Meth Enzymol 113:379–390

    Article  PubMed  CAS  Google Scholar 

  • Smith PK, Krohn RI, Hemanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76–85

    Article  PubMed  CAS  Google Scholar 

  • Stephensen E, Sturve J, Förlin L (2002) Effects of redox cycling compounds on glutathione content and activity of glutathione-related enzymes in rainbow trout liver. Comp Biochem Physiol C 133:435–442. doi: 10.1016/S1532-0456(02)00129-1

    Google Scholar 

  • Stevens ED, Devlin RH (2000) Intestinal morphology in growth hormone transgenic coho salmon. J Fish Biol 56:191–195. doi: 10.1111/j.1095-8649.2000.tb02094.x

    Google Scholar 

  • Stevens ED, Devlin RH (2005) Gut size in GH-transgenic coho salmon is enhanced by both the GH transgene and increased food intake. J Fish Biol 66:1633–1648. doi: 10.1111/j.1095-8649.2005.00707.x

    Google Scholar 

  • Szkudelski T, Okulicz M, Bialik I, Szkudelska K (2004) The influence of fasting on liver sulfhydryl groups, glutathione peroxidase and glutathione-S-transferase activities in the rat. J Physiol Biochem 60:1–6

    Article  PubMed  CAS  Google Scholar 

  • Zhu Z, Mukhina S, Zhu T, Mertani HC, Lee K-O, Lobie PE (2005) p44/42 MAP kinase-dependent regulation of catalase by autocrine human growth hormone protects human mammary carcinoma cells from oxidative stress-induced apoptosis. Oncogene 34:3774–3785. doi: 10.1038/sj.onc.1208541

    Google Scholar 

Download references

Acknowledgments

This project was supported by a Canadian Regulatory System for Biotechnology grant to RH Devlin, and Natural Sciences and Engineering Research Council of Canada (NSERC) grants to CJ Brauner and GK Iwama. We are indebted to Dionne Sakhrani and Carlo Biagi for assistance with this project, Dr. Patricia Schulte for feedback on this project, and to Dr. Matthew Rise for supplying gene array data. This experiment complied with current laws of the country (Canada) in which experiments were performed.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Robert H. Devlin.

Additional information

Communicated by H.V. Carey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Leggatt, R.A., Brauner, C.J., Iwama, G.K. et al. The glutathione antioxidant system is enhanced in growth hormone transgenic coho salmon (Oncorhynchus kisutch). J Comp Physiol B 177, 413–422 (2007). https://doi.org/10.1007/s00360-006-0140-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00360-006-0140-5

Keywords

Navigation