Abstract
In order to know if insulin-like signalling is involved in the control of oxidative stress in mammalian tissues in relation to aging, ad libitum-fed and caloric restricted Wistar rats were treated during 2 weeks with GH and insulin. The most consistent effect of the hormonal treatments was an increase in plasma IGF-1 levels. Caloric restriction during 6 weeks decreased ROS generation and oxidative DNA damage in heart mitochondria and this was reversed by insulin treatment. The decrease in oxidative damage to liver nuclear DNA induced by caloric restriction was also reversed by GH and insulin. In the liver, however, insulin and GH decreased mitochondrial ROS generation while they increased oxidative damage to mitochondrial DNA. GH and insulin decreased three different markers of oxidative modification of liver proteins, while they increased lipoxidation-dependent markers. This last result is related to the increase in phospholipid unsaturation induced in the liver by both hormones. The results suggest that the idea that insulin-like signalling controls oxidative stress in mammals cannot be generalized since both prooxidant and protective effects of GH and insulin are observed depending on the particular parameter and tissue selected.
Similar content being viewed by others
Abbreviations
- AA:
-
antimycin A
- ASA:
-
aminoadipic semialdehyde
- CML:
-
Nɛ-(carboxymethyl)lysine
- CEL:
-
Nɛ-(carboxyethyl)lysine
- DBI:
-
double bond index
- dG:
-
deoxyguanosine
- FA:
-
fatty acids
- GSA:
-
glutamic semialdehyde
- MDAL:
-
Nɛ-(malondialdehyde)lysine
- mtDNA:
-
mitochondrial DNA
- nDNA:
-
nuclear DNA
- ROS:
-
reactive oxygen species
- ROT:
-
rotenone
- 8-oxodG:
-
8-oxo,7,8-dihydro-2’-deoxyguanosine
References
MU Ahmed E Brinkmann-Frye TP Degenhardt SR Thorpe JW Baynes (1997) ArticleTitle Nepsilon-(carboxyethyl)lysine, a product of the chemical modification of proteins by methylglyoxal, increases with age in human lens proteins Biochem J 324 565–570 Occurrence Handle9182719 Occurrence Handle1:CAS:528:DyaK2sXjvFGmtLc%3D
JG Asunción A Millan R Pla L Bruseghini A Esteras FV Pallardo J Sastre J Viña (1996) ArticleTitleMitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA FASEB J 10 333–338 Occurrence Handle8641567
I Azcoitia M Perez-Martin V Salazar C Castillo C Ariznavarreta LM Garcia-Segura JAF Tresguerres (2004) ArticleTitleGH prevents neuronal loss in the aged hippocampus Neurobiol Aging 26 697–703
P Bang B Kerstin RG Rosenfeld K Hall (1994) ArticleTitleFasting affects serum IGFs and IGF binding proteins differentially in patients with non insulin dependent diabetes mellitus versus healthy obese and non obese subjects J Clin Endocrinol Metab 78 960–967 Occurrence Handle7512573 Occurrence Handle1:STN:280:DyaK2c3gvFeruw%3D%3D
G Barja (2002) ArticleTitleThe quantitative measurement of H2O2 generation in isolated mitochondria J Bioenerg Biomembr 34 227–233 Occurrence Handle12171072 Occurrence Handle1:CAS:528:DC%2BD38XkvFejs7c%3D
G Barja (2004) ArticleTitleAging in vertebrates and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism Biol Rev 79 235–251 Occurrence Handle15191224
M Bluher BB Kahn CR Khan (2003) ArticleTitleExtended longevity in mice lacking the insulin receptor in adipose tissue Science 299 572–574 Occurrence Handle12543978
HM Brown-Borg KE Borg CJ Meliska A Bartke (1996) ArticleTitleDwarf mice and the ageing process Nature 384 33 Occurrence Handle8900272 Occurrence Handle1:CAS:528:DyaK28XmvVWrsbs%3D
C Castillo M Cruzado C Ariznavarreta P Gil-loyzaga V Lahere V Cachofeiro JAF Tresguerres (2003) ArticleTitleBody composition and vascular effects of growth hormone administration in old female rats Exp Gerontol 38 971–979 Occurrence Handle12954484 Occurrence Handle1:CAS:528:DC%2BD3sXmvVygtrc%3D
DJ Clancy D Gems LG Harshman S Oldham H Stocker E Hafen SJ Leevers L Partridge (2001) ArticleTitleExtension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein Science 292 104–106 Occurrence Handle11292874 Occurrence Handle1:CAS:528:DC%2BD3MXis1Grtrc%3D
KT Coshigano D Clemmons LL Bellush JJ Kopchick (2000) ArticleTitleAssessment of growth parameters and life span of GHR/BP gene-disrupted mice Endocrinology 141 2608–2613
K Flurkey J Papaconstantinou RA Miller DE Harrison (2001) ArticleTitleLifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production Proc Natl Acad Sci USA 98 6736–6741 Occurrence Handle11371619 Occurrence Handle1:CAS:528:DC%2BD3MXksVOkurc%3D
J Folch M Lees GH Sloane-Stanley (1957) ArticleTitleA simple method for the isolation and purification of total lipids from animal tissues J Biol Chem 226 497–509 Occurrence Handle13428781 Occurrence Handle1:STN:280:DyaG2s%2FnsFCjtw%3D%3D
RA French SR Broussard WA Meir C Minshall S Arkins JF Zachary R Dantzer KW Kelley (2002) ArticleTitleAge-associated loss of bone marrow hematopoietic cells is reversed by GH and accompanies thymic reconstitution Endocrinology 143 690–699 Occurrence Handle11796526 Occurrence Handle1:CAS:528:DC%2BD38XosFajtA%3D%3D
MX Fu JR Requena AJ Jenkins TJ Lyons JW Baynes SR Thorpe (1996) ArticleTitleThe advanced glycation end product, N ɛ-(Carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions J Biol Chem 271 9982–9986 Occurrence Handle8626637 Occurrence Handle1:CAS:528:DyaK28XisFGqtbs%3D
R Gredilla A Sanz M López-Torres G Barja (2001) ArticleTitleCaloric restriction decreases mitochondrial free radical generation at Complex I and lowers oxidative damage to mitochondrial DNA in the rat heart FASEB J 15 1589–1591 Occurrence Handle11427495 Occurrence Handle1:CAS:528:DC%2BD3MXlvFantbg%3D
V Herbert KS Iau CW Gotlieb SJ Bleicher (1965) ArticleTitleCoated charcoal immunoassay of insulin J Clin Endocrinol Metab 25 1375–1384 Occurrence Handle5320561 Occurrence Handle1:CAS:528:DyaF2MXltVSmtL0%3D Occurrence Handle10.1210/jcem-25-10-1375
M Holzenberg J Dupont B Ducos P Leneuve A Geloen PC Even P Cervera Y Le Bouc (2003) ArticleTitleIGF-1 receptor regulates lifespan and resistance to oxidative stress in mice Nature 421 182–187
WM Hunter FG Greewood (1962) ArticleTitlePreparation of iodine-131 labelled human growth hormone of high specific activity Nature (London) 194 495–496 Occurrence Handle1:STN:280:DyaF38%2FltFCrsw%3D%3D
OGP Isaksson A Lindahl A Nilsson J Isgaard (1987) ArticleTitleMechanism of the stimulatory effect of GH on longitudinal bone Endocr Rev 8 426–438 Occurrence Handle3319530 Occurrence Handle1:CAS:528:DyaL1cXkvFeluw%3D%3D Occurrence Handle10.1210/edrv-8-4-426
A Jensen G Calvayrac B Karahalil VA Bohr T Stevnsner (2003) ArticleTitleMammalian 8-oxoguanine DNA glycosilase 1 incises 8-oxoadenine opposite cytosine in nuclei and mitochondria, while a different glycosylase incises 8-oxoadenine opposite guanine in nuclei J Biol Chem 278 19541–19548 Occurrence Handle12644468 Occurrence Handle1:CAS:528:DC%2BD3sXjvVSktLs%3D
JOL Jorgensen WE Blum N Moller MB Ranke JS Christianssen (1991) ArticleTitleShort term changes in serum IGFs and IGF binding protein 3 after different modes of intravenous GH exposure in GH deficient patients J Clin Endocr Metab 72 582–589 Occurrence Handle1705258 Occurrence Handle1:STN:280:DyaK3M7kslGhuw%3D%3D
MA Kaluzny LA Duncan MV Merrit DE Epps (1985) ArticleTitleRapid separation of lipid classes in high yield and purity using bonded phase columns J Lipid Res 26 135–140 Occurrence Handle3973509 Occurrence Handle1:CAS:528:DyaL2MXhs1eitrc%3D
C Kenyon (2001) ArticleTitleA conserved regulatory system for aging Cell 105 165–168 Occurrence Handle11336665 Occurrence Handle1:CAS:528:DC%2BD3MXjtFOkt7w%3D
KJ Knecht JA Dunn KF McFarland DR McCance TJ Lyons SR Thorpe JW Baynes (1991) ArticleTitleEffects of diabetes and aging on Ne-(Carboxymethyl)lysine levels in human urine Diabetes 40 190–196 Occurrence Handle1899406 Occurrence Handle1:STN:280:DyaK3M7it1ClsQ%3D%3D
AJ Lambert BJ Merry (2004) ArticleTitleEffect of caloric restriction on mitochondrial reactive oxygen species production and bioenergetics: reversal by insulin Am J Physiol 286 R71–R79 Occurrence Handle1:CAS:528:DC%2BD2cXot1Smsg%3D%3D
A Latorre A Moya A Ayala (1986) ArticleTitleEvolution of mitochondrial DNA in Drosophila suboscura Proc Natl Acad Sci USA 83 8649–8653 Occurrence Handle16578796 Occurrence Handle1:CAS:528:DyaL2sXhsVWisw%3D%3D
RJ Lichtenwalner ME Forbes SA Bennet CD Lynch WE Sonntag DR Riddle (2001) ArticleTitleIntracerebroventricluar infusion of insulin-like growth factor-1 ameliorates the age related decline in hippocampal neurogenesis Neuroscience 107 603–613 Occurrence Handle11720784 Occurrence Handle1:CAS:528:DC%2BD3MXosFKnsLo%3D
L Lima V Arce JAF Tresguerres J Devesa (1993) ArticleTitleClonidine potentiates the GH response to GHRH in norepinephrine synthesis-inhibited rats Neuroendocrinol 57 1155–1169 Occurrence Handle1:STN:280:DyaK2c%2FltVCjsw%3D%3D
S Loft HE Poulsen (1999) ArticleTitleMarkers of oxidative damage to DNA: antioxidants and molecular damage Meth Enzymol 300 166–184 Occurrence Handle10.1016/S0076-6879(99)00124-X Occurrence Handle9919520 Occurrence Handle1:CAS:528:DyaK1MXltVOj
M López-Torres R Gredilla A Sanz G Barja (2002) ArticleTitleInfluence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria Free Rad Biol Med 32 882–889 Occurrence Handle11978489
D Maiter T Fliesen LE Underwood (1989) ArticleTitleDietary protein restriction decreases IGF-1 independent of insulin and liver GH binding Endocrinology 129 2604–2611
AL Markowska M Mooney WE Sonntag (1998) ArticleTitleInsulin-like groth factor-I (IGF-1) ameliorates age-related behavioral deficits Neurosci 87 559–569 Occurrence Handle1:CAS:528:DyaK1cXlslGju78%3D
R Pamplona M Portero-Otín J Requena R Gredilla G Barja (2002) ArticleTitleOxidative, glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after four months of caloric restriction than in age-matched controls Mech Ageing Develop 123 1437–1446 Occurrence Handle1:CAS:528:DC%2BD38XosFeqsrg%3D
MA Papadakis D Grady D Black MJ Tierney GA Gooding M Schambelan C Grunfeld (1996) ArticleTitleGrowth hormone replacement in healthy older men improves body composition but not functional ability Ann Intern Med 124 708–716 Occurrence Handle8633830 Occurrence Handle1:CAS:528:DyaK28XislOisrw%3D
JR Requena MX Fu MU Ahmed AJ Jenkins TJ Lyons JW Baynes SR Thorpe (1997) ArticleTitleQuantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoproteins Biochem J 322 317–325 Occurrence Handle9078279 Occurrence Handle1:CAS:528:DyaK2sXhslKqsrs%3D
JR Requena CC Chao RL Levine ER Stadtman (2001) ArticleTitleGlutamic and aminoadipic semialdehydes are the main carbonyl products of metal catalyzed oxidation of proteins PNAS 98 69–74 Occurrence Handle11120890 Occurrence Handle1:CAS:528:DC%2BD3MXkslKlsQ%3D%3D
MA Rolde Lama A Perez Romero JAF Tresguerres M Hermanussen C Ariznavarreta (2000) ArticleTitleRecombinant GH enhances tibial growth in peripubertal females but not in males Eur J Endocrinol 142 517–523 Occurrence Handle1:CAS:528:DC%2BD3cXjslelsrY%3D
A Sanz A Bartke G Barja (2002) ArticleTitleLong-lived Ames dwarf mice: oxidative damage to mitochondrial DNA in heart and brain J Am Aging Assoc 25 119–122 Occurrence Handle1:CAS:528:DC%2BD3sXjtlOgt7k%3D
RS Sohal HH Ku S Agarwal MJ Forster H Lal (1994) ArticleTitleOxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse Mech Ageing Dev 74 121–133 Occurrence Handle7934203 Occurrence Handle1:CAS:528:DyaK2cXlsFCjtLo%3D
WE Sonntag C Lynch P Thornton A Khan S Bennett R Ingram (2000) ArticleTitleThe effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain aging J Anat 4 575–585
E Wolf E Kahnt J Ehrlein W Hermanns G Brem R Wanke (1993) ArticleTitleEffects of long-termelevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models Mech Ageing Dev 68 71–87 Occurrence Handle8350664 Occurrence Handle1:CAS:528:DyaK3sXkvVKktrg%3D
H Yamaza T Chiba Y Higami I Shimokawa (2002) ArticleTitleLifespan extension by caloric restriction: an aspect of energy metabolism Microsc Res Techn 59 325–330
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sanz, A., Gredilla, R., Pamplona, R. et al. Effect of insulin and growth hormone on rat heart and liver oxidative stress in control and caloric restricted animals. Biogerontology 6, 15–26 (2005). https://doi.org/10.1007/s10522-004-7380-0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s10522-004-7380-0