Abstract
Caloric restriction (CR) is known as the only non-genetic method proven to slow the rate of aging and extend lifespan in animals. Free radicals production emerges from normal metabolic activity and generates the accumulation of oxidized macromolecules, one of the main characteristics of aging. Due to its central role in cell bioenergetics, a great interest has been paid to CR-induced modifications in mitochondria, where CR has been suggested to decrease reactive oxygen species production. The plasma membrane contains a trans-membrane redox system (PMRS) that provides electrons to recycle lipophilic antioxidants, such as α-tocopherol and coenzyme Q (CoQ), and to modulate cytosolic redox homeostasis. In the present study, we have investigated age differences in the PMRS in mouse liver and their modulation by CR. Aging induced a decrease in the ratio of CoQ10/CoQ9 and α-tocopherol in liver PM from AL-fed mice that was attenuated by CR. CoQ-dependent NAD(P)H dehydrogenases highly increased in CR old mice liver PMs. On the other hand, the CoQ-independent NADH-FCN reductase activity increased in AL-fed animals; whereas, in mice under CR this activity did not change during aging. Our results suggest that liver PMRS activity changes during aging and that CR modulates these changes. By this mechanism CR maintains a higher antioxidant capacity in liver PM of old animals by increasing the activity of CoQ-dependent reductases. Also, the putative role of PMRS in the modulation of redox homeostasis of cytosol is implicated.
Key words: cytochrome b5 reductase, plasma membrane redox system, quinone reductase, ubiquinone
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References
- Alcain FJ, Buron MI, Villalba JM, Navas P. Ascorbate is regenerated by HL-60 cells through the transplasmalemma redox system. Biochim Biophys Acta. 1991;1073(2):380–385. doi: 10.1016/0304-4165(91)90146-8. [DOI] [PubMed] [Google Scholar]
- Armeni T, Principato G, Quiles JL, Pieri C, Bompadre S, Battino M. Mitochondrial dysfunctions during aging: Vitamin E deficiency or caloric restriction-two different ways of modulating stress. J Bioenerg Biomembranes. 2003;35(2):181–191. doi: 10.1023/A:1023754305218. [DOI] [PubMed] [Google Scholar]
- Barja G. Endogenous oxidative stress: Relationship to aging, longevity and caloric restriction. Ageing Res Rev. 2002;1(3):397–411. doi: 10.1016/S1568-1637(02)00008-9. [DOI] [PubMed] [Google Scholar]
- Beyer RE. The role of ascorbate in antioxidant protection of biomembranes: Interaction with vitamin E and coenzyme Q. J Bioenerg Biomembranes. 1994;26(4):349–358. doi: 10.1007/BF00762775. [DOI] [PubMed] [Google Scholar]
- Beyer RE, Segura-Aguilar J, Bernardo S, Cavazzoni M, Fato R, Fiorentini D, et al. The role of DT-diaphorase in the maintenance of the reduced antioxidant form of coenzyme Q in membrane systems. Proc Natl Acad Sci USA. 1996;93(6):2528–2532. doi: 10.1073/pnas.93.6.2528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein–dye binding. Anal Biochem. 1976;72:248–254. doi: 10.1016/0003-2697(76)90527-3. [DOI] [PubMed] [Google Scholar]
- Burón MI, Rodríguez-Aguilera JC, Alcaín FJ, Navas P. Transplasma membrane redox system in HL-60 cells is modulated during TPA-induced differentiation. Biochem Biophys Res Commun. 1993;192(2):439–445. doi: 10.1006/bbrc.1993.1434. [DOI] [PubMed] [Google Scholar]
- Crane FL, Sun IL, Clark MG, Grebing C. Transplasma–membrane redox systems in growth and development. Biochim Biophys Acta. 1985;811:233–264. doi: 10.1016/0304-4173(85)90013-8. [DOI] [PubMed] [Google Scholar]
- Crane FL, Sun IL, Barr R, Low H. Electron and proton transport across the plasma membrane. J Bioenerg Biomembranes. 1991;23(5):773–803. doi: 10.1007/BF00786001. [DOI] [PubMed] [Google Scholar]
- Cabo R, Furer-Galban S, Anson RM, Gilman C, Gorospe M, Lane MA. An in vitro model of caloric restriction. Exp Gerontol. 2003;38(6):631–639. doi: 10.1016/S0531-5565(03)00055-X. [DOI] [PubMed] [Google Scholar]
- Cabo R, Cabello R, Rios M, Lopez-Lluch G, Ingram DK, Lane MA, et al. Calorie restriction attenuates age-related alterations in the plasma membrane antioxidant system in rat liver. Exp Gerontol. 2004;39(3):297–304. doi: 10.1016/j.exger.2003.12.003. [DOI] [PubMed] [Google Scholar]
- Grey ADNJ. A proposed mechanism for the lowering of mitochondrial electron leak by caloric restriction. Mitochondrion. 2001;1(2):129–139. doi: 10.1016/S1567-7249(01)00008-3. [DOI] [PubMed] [Google Scholar]
- Castillo-Olivares A, Nunez de Castro I, Medina MA. Dual role of plasma membrane electron transport systems in defense. Crit Rev Biochem Mol Biol. 2000;35(3):197–220. doi: 10.1080/10409230091169203. [DOI] [PubMed] [Google Scholar]
- Fernandez-Ayala DJ, Martin SF, Barroso MP, Gomez-Diaz C, Villalba JM, Rodriguez-Aguilera JC, et al. Coenzyme Q protects cells against serum withdrawal-induced apoptosis by inhibition of ceramide release and caspase-3 activation. Antioxid Redox Signal. 2000;2(2):263–275. doi: 10.1089/ars.2000.2.2-263. [DOI] [PubMed] [Google Scholar]
- Finkel T, Holbrook N. Oxidants, oxidative stress and the biology of ageing. Nature. 2000;408:239–247. doi: 10.1038/35041687. [DOI] [PubMed] [Google Scholar]
- Forster MJ, Sohal BH, Sohal RS. Reversible effects of long-term caloric restriction on protein oxidative damage. J Gerontol, A, Biol Sci Med Sci. 2000;55(11):B522–B529. doi: 10.1093/gerona/55.11.b522. [DOI] [PubMed] [Google Scholar]
- Gomez-Diaz C, Rodriguez-Aguilera JC, Barroso MP, Villalba JM, Navarro F, Crane FL, et al. Antioxidant ascorbate is stabilized by NADH-coenzyme Q10 reductase in the plasma membrane. J Bioenerg Biomembranes. 1997;29(3):251–257. doi: 10.1023/A:1022410127104. [DOI] [PubMed] [Google Scholar]
- Gomez-Diaz C, Villalba JM, Perez-Vicente R, Crane FL, Navas P. Ascorbate stabilization is stimulated in rho(0)HL-60 cells by CoQ10 increase at the plasma membrane. Biochem Biophys Res Commun. 1997;234(1):79–81. doi: 10.1006/bbrc.1997.6582. [DOI] [PubMed] [Google Scholar]
- Gredilla R, Lopez-Torres M, Barja G. Effect of time of restriction on the decrease in mitochondrial H2O2 production and oxidative DNA damage in the heart of food-restricted rats. Microsc Res Tech. 2002;59(4):273–277. doi: 10.1002/jemt.10204. [DOI] [PubMed] [Google Scholar]
- Harman D. Aging: A theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300. doi: 10.1093/geronj/11.3.298. [DOI] [PubMed] [Google Scholar]
- Jeon TI, Lim BO, Yu BP, Lim Y, Jeon EJ, Park DK. Effect of dietary restriction on age-related increase of liver susceptibility to peroxidation in rats. Lipids. 2001;36(6):589–593. doi: 10.1007/s11745-001-0761-1. [DOI] [PubMed] [Google Scholar]
- Kagan VE, Serbinova EA, Packer L. Recycling and antioxidant activity of tocopherol homologs of differing hydrocarbon chain lengths in liver microsomes. Arch Biochem Biophys. 1990;282(2):221–225. doi: 10.1016/0003-9861(90)90108-B. [DOI] [PubMed] [Google Scholar]
- Kagan VE, Serbinova EA, Packer L. Generation and recycling of radicals from phenolic antioxidants. Arch Biochem Biophys. 1990;280(1):33–39. doi: 10.1016/0003-9861(90)90514-Y. [DOI] [PubMed] [Google Scholar]
- Kagan VE, Nohl H, Quinn PJ. Coenzyme Q: Its role in scavenging and generation of radicals in membranes. In: Cadenas E, Packer L, editors. Handbook of Antioxidants. New York: Marcel Decker; 1996. pp. 157–201. [Google Scholar]
- Larm JA, Vaillant F, Linnane AW, Lawen A. Up-regulation of the plasma membrane oxidoreductase as a prerequisite for the viability of human Namalwa cells. J Biol Chem. 1994;296:30097–30100. [PubMed] [Google Scholar]
- Larsen PL. Aging and resistance to oxidative damage in Caenorhabditis elegans. Proc Natl Acad Sci USA. 1993;90(19):8905–8909. doi: 10.1073/pnas.90.19.8905. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lass A, Sohal BH, Weindruch R, Forster MJ, Sohal RS. Caloric restriction prevents age-associated accrual of oxidative damage to mouse skeletal muscle mitochondria. Free Radic Biol Med. 1998;25(9):1089–1097. doi: 10.1016/S0891-5849(98)00144-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lin SJ, Kaeberlein M, Andalis AA, Sturtz LA, Defossez PA, Culotta VC, et al. Calorie restriction extends Saccharomyces cerevisiae lifespan by increasing respiration. Nature. 2002;418(6895):344–348. doi: 10.1038/nature00829. [DOI] [PubMed] [Google Scholar]
- Lopez-Lluch G, Buron MI, Alcain FJ, Quesada JM, Navas P. Redox regulation of cAMP levels by ascorbate in 1,25-dihydroxy-vitamin D3-induced differentiation of HL-60 cells. Biochem J. 1998;331(Pt 1):21–27. doi: 10.1042/bj3310021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lopez-Torres M, Gredilla R, Sanz A, Barja G. Influence of aging and long-term caloric restriction on oxygen radical generation and oxidative DNA damage in rat liver mitochondria. Free Radic Biol Med. 2002;32(9):882–889. doi: 10.1016/S0891-5849(02)00773-6. [DOI] [PubMed] [Google Scholar]
- Martin SF, Gomez-Diaz C, Bello RI, Navas P, Villalba JM. Inhibition of neutral Mg2+-dependent sphingomyelinase by ubiquinol-mediated plasma membrane electron transport. Protoplasma. 2003;221(1–2):109–116. doi: 10.1007/s00709-002-0070-3. [DOI] [PubMed] [Google Scholar]
- Martinus RD, Linnane AW, Nagley P. Growth of rho 0 human Namalwa cells lacking oxidative phosphorylation can be sustained by redox compounds potassium ferricyanide or coenzyme Q10 putatively acting through the plasma membrane oxidase. Biochem Mol Biol Int. 1993;31(6):997–1005. [PubMed] [Google Scholar]
- Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, et al. Extension of life-span with superoxide dismutase/catalase mimetics. Science. 2000;289(5484):1567–1569. doi: 10.1126/science.289.5484.1567. [DOI] [PubMed] [Google Scholar]
- Merker MP, Olson LE, Bongard RD, Patel MK, Linehan JH, Dawson CA. Ascorbate-mediated transplasma membrane electron transport in pulmonary arterial endothelial cells. Am J Physiol. 1998;274(5 Pt 1):L685–L693. doi: 10.1152/ajplung.1998.274.5.L685. [DOI] [PubMed] [Google Scholar]
- Migliaccio E, Giorgio M, Mele S, Pelicci G, Reboldi P, Pandolfi PP, et al. The p66shc adaptor protein controls oxidative stress response and life span in mammals [see comments] Nature. 1999;402(6759):309–313. doi: 10.1038/46311. [DOI] [PubMed] [Google Scholar]
- Navas P, Sun IL, Morre DJ, Crane FL. Decrease of NADH in HeLa cells in the presence of transferrin or ferricyanide. Biochem Biophys Res Commun. 1986;135(1):110–115. doi: 10.1016/0006-291X(86)90949-6. [DOI] [PubMed] [Google Scholar]
- Navas P, Nowack DD, Morre DJ. Isolation of purified plasma membranes from cultured cells and hepatomas by two-phase partition and preparative free-flow electrophoresis. Cancer Res. 1989;49(8):2147–2156. [PubMed] [Google Scholar]
- Pamplona R, Portero-Otin M, Requena J, Gredilla R, Barja G. Oxidative, glycoxidative and lipoxidative damage to rat heart mitochondrial proteins is lower after 4 months of caloric restriction than in age-matched controls. Mech Ageing Dev. 2002;123(11):1437–1446. doi: 10.1016/S0047-6374(02)00076-3. [DOI] [PubMed] [Google Scholar]
- Rafique R, Schapira AH, Coper JM. Mitochondrial respiratory chain dysfunction in ageing; influence of vitamin E deficiency. Free Radic Res. 2004;38(2):157–165. doi: 10.1080/10715760310001643311. [DOI] [PubMed] [Google Scholar]
- Raha S, Robinson BH. Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci. 2000;25(10):502–508. doi: 10.1016/S0968-0004(00)01674-1. [DOI] [PubMed] [Google Scholar]
- Rodriguez-Aguilera JC, Nakayama K, Arroyo A, Villalba JM, Navas P. Transplasma membrane redox system of HL-60 cells is controlled by cAMP. J Biol Chem. 1993;268(35):26346–26349. [PubMed] [Google Scholar]
- Santos-Ocana C, Villalba JM, Cordoba F, Padilla S, Crane FL, Clarke CF, et al. Genetic evidence for coenzyme Q requirement in plasma membrane electron transport. J Bioenerg Biomembranes. 1998;30(5):465–475. doi: 10.1023/A:1020542230308. [DOI] [PubMed] [Google Scholar]
- Slater AF, Stefan C, Nobel I, Dobbelsteen DJ, Orrenius S. Signalling mechanisms and oxidative stress in apoptosis. Toxicol Lett. 1995;82–83:149–153. doi: 10.1016/0378-4274(95)03474-9. [DOI] [PubMed] [Google Scholar]
- Sohal RS, Ku HH, Agarwal S, Forster MJ, Lal H. Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse. Mech Ageing Dev. 1994;74(1–2):121–133. doi: 10.1016/0047-6374(94)90104-X. [DOI] [PubMed] [Google Scholar]
- Sun IL, Navas P, Crane FL, Chou JY, Low H. Transplasmalemma electron transport is changed in simian virus 40 transformed liver cells. J Bioenerg Biomembranes. 1986;18(6):471–485. doi: 10.1007/BF00743145. [DOI] [PubMed] [Google Scholar]
- Sun IL, Sun EE, Crane FL, Morre DJ. Evidence for coenzyme Q function in transplasma membrane electron transport. Biochem Biophys Res Commun. 1990;172(3):979–984. doi: 10.1016/0006-291X(90)91542-Z. [DOI] [PubMed] [Google Scholar]
- Villalba JM, Canalejo A, Rodriguez-Aguilera JC, Buron MI, Moore DJ, Navas P. NADH-ascorbate free radical and -ferricyanide reductase activities represent different levels of plasma membrane electron transport. J Bioenerg Biomembranes. 1993;25(4):411–417. doi: 10.1007/BF00762467. [DOI] [PubMed] [Google Scholar]
- Villalba JM, Navarro F, Cordoba F, Serrano A, Arroyo A, Crane FL, et al. Coenzyme Q reductase from liver plasma membrane: purification and role in trans-plasma-membrane electron transport. Proc Natl Acad Sci USA. 1995;92(11):4887–4891. doi: 10.1073/pnas.92.11.4887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yu BP. Free Radicals in Aging. Boca Raton, FL: CRC; 1994. [Google Scholar]
- Zainal TA, Oberley TD, Allison DB, Szweda LI, Weindruch R. Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle. FASEB J. 2000;14(12):1825–1836. doi: 10.1096/fj.99-0881com. [DOI] [PubMed] [Google Scholar]
