Abstract
A low rate of mitochondrial ROS production (mitROSp) and a low degree of fatty acid unsaturation are characteristic traits of long-lived animals and can be obtained in a single species by methionine restriction (MetR) or atenolol (AT) treatments. However, simultaneous application of both treatments has never been performed. In the present investigation it is shown that MetR lowers mitROSp and complex I content. Both the MetR and the AT treatments lower protein oxidative modification and oxidative damage to mtDNA and the fatty acid unsaturation degree in rat heart mitochondria. The decrease in fatty acid unsaturation seems to be due, at least in part, to decreases in desaturase and elongase activities or peroxisomal β-oxidation. Furthermore, the phosphorylation of extracellular signal-regulated kinase (ERK) was stimulated by MetR and AT. The decrease in membrane fatty acid unsaturation and protein oxidation, and the changes in fatty acids and p-ERK showed additive effects of both treatments. In addition, the increase in mitROSp induced by AT observed in the present investigation was totally avoided with the combined MetR + AT treatment. It is concluded that the simultaneous treatment with MetR plus atenolol is more beneficial than either single treatment alone to lower oxidative stress in rat heart mitochondria, analogously to what has been reported in long-lived animal species.
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Albring M, Griffith J, Attardi G (1977) Association of a protein structure of probable membrane derivation with HeLa cell mitochondrial DNA near its origin of replication. PNAS 74:1348–1352
Asunción JG, Millan A, Pla R, Bruseghini L, Esteras A, Pallardo FV, Sastre J, Viña J (1996) Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial DNA. FASEB J 10:333–338
Barja G (2002) The quantitative measurement of H2O2 generation in isolated mitochondria. J Bioenerg Biomembr 34:227–233
Barja G (2004a) Aging in vertebrates and the effect of caloric restriction: a mitochondrial free radical production-DNA damage mechanism? Biol Rev 79:235–251
Barja G (2004b) Free radicals and aging. Trends Neurosci 27:595–600
Bell EL, Guarente L (2011) The SirT3 divining rod points to oxidative stress. Mol Cell 42:561–568
Caro P, Gomez J, Lopez-Torres M, Sanchez I, Naudi A, Jove M, Pamplona R, Barja G (2008) Forty percent and eighty percent methionine restriction decrease mitochondrial ROS generation and oxidative stress in rat liver. Biogerontology 9:183–196
Caro P, Gomez J, Sanchez I, Naudi A, Ayala V, López-Torres M, Pamplona R, Barja G (2009) Forty percent methionine restriction decreases mitochondrial oxygen radical production and leak at complex I during forward electron flow and lowers oxidative damage to proteins and mitochondrial DNA in rat kidney and brain mitochondria. Rejuv Res 12:421–434
Dhabi JM, Monte PL, Wingo J, Rowley BC, Cao SX, Waldford RL, Spindler SR (2001) Caloric restriction alters the feeding response of key metabolic enzyme genes. Mech Ageing Dev 122:1033–1048
Gredilla R, Barja G (2005) The role of oxidative stress in relation to caloric restriction and longevity. Endocrinology 146:3713–3717
Guillou H, Zadravec D, Martin PG, Jacobsson A (2010) The key roles of elongases and desaturases in mammalian fatty acid metabolism: insights from transgenic mice. Prog Lipid Res 49:186–199
Harman D (1972) The biological clock: the mitochondria. J Am Geriatr Soc 20:145–147
Holt IJ, He J, Mao C, Boyd-Kirkup JD, Martinsson P, Sembongi H, Reyes A, Spelbrnk JN (2007) Mammalian mitochondrial nucleoids: organizing an independently minded genome. Mitochondrion 7:311–321
Hulbert AJ, Pamplona R, Buffenstein R, Buttemer WA (2007) Life and death: metabolic rate, membrane composition, and life span of animals. Physiol Rev 87:1175–1213
Kalhan SC, Uppal SO, Moorman JL, Bennett C, Gruca LL, Parimi PS, Dasarathy S, Serre D, Hanson RW (2011) Metabolic and genomic response to dietary isocaloric protein restriction in the rat. J Biol Chem 286:5266–5277
Latorre A, Moya A, Ayala A (1986) Evolution of mitochondrial DNA in Drosophila suboscura. PNAS 83:8649–8653
Lopez-Torres M, Barja G (2008) Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans. Biochim Biophys Acta 1780:1337–1347
Mela L, Seitz S (1997) Isolation of mitochondria with emphasis on heart mitochondria from small amounts of tissue. Methods Enzymol 55:39–46
Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, Smith-Wheelock M (2005) Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4:119–125
Orentreich N, Matias JR, DeFelice A, Zimmerman JA (1993) Low methionine ingestion by rats extends life span. J Nutr 123:269–274
Pamplona R (2011) Advanced lipoxidation end-products. Chem Biol Interact 192:14–20
Pamplona R, Barja G (2006) Mitochondrial oxidative stress, aging and caloric restriction: the protein and methionine connection. Biochim Biophys Acta 1757:496–508
Pamplona R, Barja G (2011) An evolutionary comparative scan for longevity-related oxidative stress resistance mechanisms in homeotherms. Biogerontology 12:409–435
Pamplona R, Barja G, Portero-Otín M (2002) Membrane fatty acid unsaturation, protection against oxidative stress, and maximum life span: a homeoviscous-longevity adaptation. Ann New York Acad Sci 959:475–490
Pamplona R, Portero-Otín M, Sanz A, Requena J, Barja G (2004) Modification of the longevity-related degree of fatty acid unsaturation modulates oxidative damage to proteins and mitochondrial DNA in liver and brain. Exper Gerontol 39:725–733
Pamplona R, Dalfó E, Ayala V, Bellmunt MJ, Prat J, Ferrer I, Portero-Otín M (2005) Proteins in human brain cortex are modified by oxidation, glycoxidation, and lipoxidation. Effects of Alzheimer disease and identification of lipoxidation targets. J Biol Chem 280:21522–21530
Perrone CE, Mattocks DAL, Plummer JD, Chittur SV, Mohney R, Vignola K, Orentreich DS, Orentreich N (2012) Genomic and metabolic responses to methionine-restricted and methionine-restricted, cysteine-supplemented diets in Fischer 344 rat inguinal adipose tissue, liver and quadriceps muscle. J Nutrigenet Nutrigenomics 5:132–157
Porter AG, Urbano AG (2006) Does apoptosis-inducing factor (AIF) have both life and death functions in cells? Bioessays 28:834–843
Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) Methionine restriction increases blood glutathione and longevity in F344 rats. FASEB J 8:1302–1307
Sanchez-Roman I, Gomez J, Naudi A, Ayala V, Portero-Otín M, Lopez-Torres M, Pamplona R, Barja G (2010) The β-blocker atenolol lowers the longevity-related degree of fatty acid unsaturation, decreases protein oxidative damage and increases ERK signaling in the heart of C57BL/6 mice. Rejuv Res 13:683–693
Sanchez-Roman I, Gomez A, Gomez J, Suarez H, Sanchez C, Naudi A, Ayala V, Portero-Otin M, Lopez-Torres M, Pamplona R, Barja G (2011) Forty percent methionine restriction lowers DNA methylation, complex I ROS generation, and oxidative damage to mtDNA and mitochondrial proteins in rat heart. J Bioenerg Biomembr 43:699–708
Sanz A, Barja G (2006) Estimation of the rate of production of oxygen radicals by mitochondria. In: Conn M (ed) Handbook of models for human aging. Academic Press, New York, pp 183–189
Someya S, Yu W, Hallows WC, Xu J, Vann JM, Leeuwenburgh C, Tanokura M, Denu JM, Prolla TA (2010) Sirt3 mediates reduction of oxidative damage and prevention of age-related hearing loss under caloric restriction. Cell 143:802–812
Sun L, Amir A, Akha S, Millar RA, Harper J (2009) Life-span extension in mice by preweaning food restriction and by methionine restriction in middle age. J Gerontol 64A:711–722
Tsai CW, Lin AH, Wang TS, Liu KL, Chen HW, Lii CK (2010) Methionine restriction up-regulates the expression of the pi class of glutathione S-transferase partially via the extracellular signal-regulated kinase activator protein-1 signaling pathway initiated by glutathione depletion. Mol Nutr Food Res 54:841–850
Verdin E, Hirschey MD, Finley LWS, Haigis MC (2010) Sirtuin regulation of mitochondria: energy production, apoptosis, and signalling. Trends Biochem Sci 35:669–675
Yan L, Vatner DE, O’Connor JP, Ivessa A, Ge H, Chen W, Hirotani S, Ishikawa Y, Sadoshima J, Vatner SF (2007) Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130:247–258
Yang SY, Hoy M, Fuller B, Sales KM, Seifalian AM, Winslet MC (2010) Pretreatment with insulin-like growth factor I protects skeletal muscle cells against oxidative damage via PI3K/Akt and ERK1/2 MAPK pathways. Lab Invest 90:391–401
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Sanchez-Roman, I., Gomez, A., Naudí, A. et al. Independent and additive effects of atenolol and methionine restriction on lowering rat heart mitochondria oxidative stress. J Bioenerg Biomembr 46, 159–172 (2014). https://doi.org/10.1007/s10863-013-9535-7
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DOI: https://doi.org/10.1007/s10863-013-9535-7