Mitochondrial Matrix Ca²⁺ Accumulation Regulates Cytosolic NAD⁺/NADH Metabolism, Protein Acetylation, and Sirtuin Expression

REFERENCES

• Thomas AP, Bird GS, Hajnoczky G, Robb-Gaspers LD, Putney JWJr. 1996. Spatial and temporal aspects of cellular calcium signaling. FASEB J. 10:1505–1517.
   PubMed Web of Science ®Google Scholar
• Denton RM, McCormack JG. 1986. The calcium sensitive dehydrogenases of vertebrate mitochondria. Cell Calcium 7:377–386. http://dx.doi.org/10.1016/0143-4160(86)90040-0.
   PubMedGoogle Scholar
• Davidson SM, Duchen MR. 2007. Endothelial mitochondria: contributing to vascular function and disease. Circ. Res. 100:1128–1141. http://dx.doi.org/10.1161/01.RES.0000261970.18328.1d.
   PubMed Web of Science ®Google Scholar
• Tarasov AI, Griffiths EJ, Rutter GA. 2012. Regulation of ATP production by mitochondrial Ca(2+). Cell Calcium 52:28–35. http://dx.doi.org/10.1016/j.ceca.2012.03.003.
   PubMed Web of Science ®Google Scholar
• Glancy B, Balaban RS. 2012. Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51:2959–2973. http://dx.doi.org/10.1021/bi2018909.
   PubMed Web of Science ®Google Scholar
• Jouaville LS, Pinton P, Bastianutto C, Rutter GA, Rizzuto R. 1999. Regulation of mitochondrial ATP synthesis by calcium: evidence for a long-term metabolic priming. Proc. Natl. Acad. Sci. U. S. A. 96:13807–13812. http://dx.doi.org/10.1073/pnas.96.24.13807.
   PubMed Web of Science ®Google Scholar
• Hajnoczky G, Robb-Gaspers LD, Seitz MB, Thomas AP. 1995. Decoding of cytosolic calcium oscillations in the mitochondria. Cell 82:415–424. http://dx.doi.org/10.1016/0092-8674(95)90430-1.
   PubMed Web of Science ®Google Scholar
• Luciani DS, Misler S, Polonsky KS. 2006. Ca2+ controls slow NAD(P)H oscillations in glucose-stimulated mouse pancreatic islets. J. Physiol. 572:379–392. http://dx.doi.org/10.1113/jphysiol.2005.101766.
   PubMed Web of Science ®Google Scholar
• Territo PR, French SA, Balaban RS. 2001. Simulation of cardiac work transitions, in vitro: effects of simultaneous Ca2+ and ATPase additions on isolated porcine heart mitochondria. Cell Calcium 30:19–27. http://dx.doi.org/10.1054/ceca.2001.0211.
   PubMedGoogle Scholar
• Borregaard N, Herlin T. 1982. Energy metabolism of human neutrophils during phagocytosis. J. Clin. Invest. 70:550–557. http://dx.doi.org/10.1172/JCI110647.
   PubMed Web of Science ®Google Scholar
• Culic O, Gruwel ML, Schrader J. 1997. Energy turnover of vascular endothelial cells. Am. J. Physiol. 273:C205–C213.
   PubMed Web of Science ®Google Scholar
• Hawkins BJ, Solt LA, Chowdhury I, Kazi AS, Abid MR, Aird WC, May MJ, Foskett JK, Madesh M. 2007. G protein-coupled receptor Ca2+-linked mitochondrial reactive oxygen species are essential for endothelial/leukocyte adherence. Mol. Cell. Biol. 27:7582–7593. http://dx.doi.org/10.1128/MCB.00493-07.
   PubMed Web of Science ®Google Scholar
• De Bock M, Wang N, Decrock E, Bol M, Gadicherla AK, Culot M, Cecchelli R, Bultynck G, Leybaert L. 2013. Endothelial calcium dynamics, connexin channels and blood-brain barrier function. Prog. Neurobiol. 108:1–20. http://dx.doi.org/10.1016/j.pneurobio.2013.06.001.
   PubMed Web of Science ®Google Scholar
• Gandhirajan RK, Meng S, Chandramoorthy HC, Mallilankaraman K, Mancarella S, Gao H, Razmpour R, Yang XF, Houser SR, Chen J, Koch WJ, Wang H, Soboloff J, Gill DL, Madesh M. 2013. Blockade of NOX2 and STIM1 signaling limits lipopolysaccharide-induced vascular inflammation. J. Clin. Invest. 123:887–902.
   PubMed Web of Science ®Google Scholar
• Ichimura H, Parthasarathi K, Quadri S, Issekutz AC, Bhattacharya J. 2003. Mechano-oxidative coupling by mitochondria induces proinflammatory responses in lung venular capillaries. J. Clin. Invest. 111:691–699. http://dx.doi.org/10.1172/JCI17271.
   PubMedGoogle Scholar
• Hu Q, Deshpande S, Irani K, Ziegelstein RC. 1999. [Ca(2+)](i) oscillation frequency regulates agonist-stimulated NF-kappaB transcriptional activity. J. Biol. Chem. 274:33995–33998. http://dx.doi.org/10.1074/jbc.274.48.33995.
   PubMed Web of Science ®Google Scholar
• Zhu L, Luo Y, Chen T, Chen F, Wang T, Hu Q. 2008. Ca2+ oscillation frequency regulates agonist-stimulated gene expression in vascular endothelial cells. J. Cell Sci. 121:2511–2518. http://dx.doi.org/10.1242/jcs.031997.
   PubMedGoogle Scholar
• Zhu L, Song S, Pi Y, Yu Y, She W, Ye H, Su Y, Hu Q. 2011. Cumulated Ca2(+) spike duration underlies Ca2(+) oscillation frequency-regulated NFkappaB transcriptional activity. J. Cell Sci. 124:2591–2601. http://dx.doi.org/10.1242/jcs.082727.
   PubMedGoogle Scholar
• Uhlen P. 2004. Spectral analysis of calcium oscillations. Sci. STKE 2004:pl15. http://dx.doi.org/10.1126/stke.2582004pl15.
   PubMedGoogle Scholar
• Palmer AE, Tsien RY. 2006. Measuring calcium signaling using genetically targetable fluorescent indicators. Nat. Protoc. 1:1057–1065. http://dx.doi.org/10.1038/nprot.2006.172.
   PubMed Web of Science ®Google Scholar
• McCombs JE, Palmer AE. 2008. Measuring calcium dynamics in living cells with genetically encodable calcium indicators. Methods 46:152–159. http://dx.doi.org/10.1016/j.ymeth.2008.09.015.
   PubMed Web of Science ®Google Scholar
• Hung YP, Albeck JG, Tantama M, Yellen G. 2011. Imaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor. Cell Metab. 14:545–554. http://dx.doi.org/10.1016/j.cmet.2011.08.012.
   PubMed Web of Science ®Google Scholar
• Hung YP, Yellen G. 2014. Live-cell imaging of cytosolic NADH-NAD+ redox state using a genetically encoded fluorescent biosensor. Methods Mol. Biol. 1071:83–95. http://dx.doi.org/10.1007/978-1-62703-622-1_7.
   PubMedGoogle Scholar
• Williamson DH, Lund P, Krebs HA. 1967. The redox state of free nicotinamide-adenine dinucleotide in the cytoplasm and mitochondria of rat liver. Biochem. J. 103:514–527.
   PubMed Web of Science ®Google Scholar
• Berridge MJ, Lipp P, Bootman MD. 2000. The versatility and universality of calcium signalling. Nat. Rev. Mol. Cell Biol. 1:11–21. http://dx.doi.org/10.1038/35036035.
   PubMed Web of Science ®Google Scholar
• Antigny F, Girardin N, Frieden M. 2012. Transient receptor potential canonical channels are required for in vitro endothelial tube formation. J. Biol. Chem. 287:5917–5927. http://dx.doi.org/10.1074/jbc.M111.295733.
   PubMed Web of Science ®Google Scholar
• Pober JS, Sessa WC. 2007. Evolving functions of endothelial cells in inflammation. Nat. Rev. Immunol. 7:803–815. http://dx.doi.org/10.1038/nri2171.
   PubMed Web of Science ®Google Scholar
• Rizzuto R, De Stefani D, Raffaello A, Mammucari C. 2012. Mitochondria as sensors and regulators of calcium signalling. Nat. Rev. Mol. Cell Biol. 13:566–578. http://dx.doi.org/10.1038/nrm3412.
   PubMed Web of Science ®Google Scholar
• McCormack JG, Denton RM. 1993. Mitochondrial Ca2+ transport and the role of intramitochondrial Ca2+ in the regulation of energy metabolism. Dev. Neurosci. 15:165–173. http://dx.doi.org/10.1159/000111332.
   PubMedGoogle Scholar
• Duchen MR. 1992. Ca(2+)-dependent changes in the mitochondrial energetics in single dissociated mouse sensory neurons. Biochem. J. 283(Part 1):41–50.
   PubMedGoogle Scholar
• Quintero M, Colombo SL, Godfrey A, Moncada S. 2006. Mitochondria as signaling organelles in the vascular endothelium. Proc. Natl. Acad. Sci. U. S. A. 103:5379–5384. http://dx.doi.org/10.1073/pnas.0601026103.
   PubMed Web of Science ®Google Scholar
• Lin SJ, Guarente L. 2003. Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. Curr. Opin. Cell Biol. 15:241–246. http://dx.doi.org/10.1016/S0955-0674(03)00006-1.
   PubMed Web of Science ®Google Scholar
• Di Lisa F, Ziegler M. 2001. Pathophysiological relevance of mitochondria in NAD(+) metabolism. FEBS Lett. 492:4–8. http://dx.doi.org/10.1016/S0014-5793(01)02198-6.
   PubMed Web of Science ®Google Scholar
• Houtkooper RH, Canto C, Wanders RJ, Auwerx J. 2010. The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. Endocr. Rev. 31:194–223. http://dx.doi.org/10.1210/er.2009-0026.
   PubMed Web of Science ®Google Scholar
• Barron JT, Gu L, Parrillo JE. 1998. Malate-aspartate shuttle, cytoplasmic NADH redox potential, and energetics in vascular smooth muscle. J. Mol. Cell. Cardiol. 30:1571–1579. http://dx.doi.org/10.1006/jmcc.1998.0722.
   PubMedGoogle Scholar
• Breitwieser GE. 2012.The intimate link between calcium sensing receptor trafficking and signaling: implications for disorders of calcium homeostasis. Mol. Endocrinol. 26:1482–1495. http://dx.doi.org/10.1210/me.2011-1370.
   PubMed Web of Science ®Google Scholar
• Houtkooper RH, Pirinen E, Auwerx J. 2012. Sirtuins as regulators of metabolism and healthspan. Nat. Rev. Mol. Cell Biol. 13:225–238. http://dx.doi.org/10.1038/nrm3293.
   PubMed Web of Science ®Google Scholar
• Lin SJ, Ford E, Haigis M, Liszt G, Guarente L. 2004. Calorie restriction extends yeast life span by lowering the level of NADH. Genes Dev. 18:12–16. http://dx.doi.org/10.1101/gad.1164804.
   PubMed Web of Science ®Google Scholar
• Revollo JR, Grimm AA, Imai S. 2004. The NAD biosynthesis pathway mediated by nicotinamide phosphoribosyltransferase regulates Sir2 activity in mammalian cells. J. Biol. Chem. 279:50754–50763. http://dx.doi.org/10.1074/jbc.M408388200.
   PubMed Web of Science ®Google Scholar
• Li X, Kazgan N. 2011. Mammalian sirtuins and energy metabolism. Int. J. Biol. Sci. 7:575–587.
   PubMed Web of Science ®Google Scholar
• Iyer A, Fairlie DP, Brown L. 2012. Lysine acetylation in obesity, diabetes and metabolic disease. Immunol. Cell Biol. 90:39–46. http://dx.doi.org/10.1038/icb.2011.99.
   PubMedGoogle Scholar
• Yuan J, Pu M, Zhang Z, Lou Z. 2009. Histone H3-K56 acetylation is important for genomic stability in mammals. Cell Cycle 8:1747–1753. http://dx.doi.org/10.4161/cc.8.11.8620.
   PubMed Web of Science ®Google Scholar
• Eskandarian HA, Impens F, Nahori MA, Soubigou G, Coppee JY, Cossart P, Hamon MA. 2013. A role for SIRT2-dependent histone H3K18 deacetylation in bacterial infection. Science 341:1238858. http://dx.doi.org/10.1126/science.1238858.
   PubMed Web of Science ®Google Scholar
• Schwer B, Schumacher B, Lombard DB, Xiao C, Kurtev MV, Gao J, Schneider JI, Chai H, Bronson RT, Tsai LH, Deng CX, Alt FW. 2010. Neural sirtuin 6 (Sirt6) ablation attenuates somatic growth and causes obesity. Proc. Natl. Acad. Sci. U. S. A. 107:21790–21794. http://dx.doi.org/10.1073/pnas.1016306107.
   PubMed Web of Science ®Google Scholar
• Yoshino J, Mills KF, Yoon MJ, Imai S. 2011. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab. 14:528–536. http://dx.doi.org/10.1016/j.cmet.2011.08.014.
   PubMed Web of Science ®Google Scholar
• Potente M, Dimmeler S. 2008. Emerging roles of SIRT1 in vascular endothelial homeostasis. Cell Cycle 7:2117–2122. http://dx.doi.org/10.4161/cc.7.14.6267.
   PubMed Web of Science ®Google Scholar
• Stein S, Matter CM. 2011. Protective roles of SIRT1 in atherosclerosis. Cell Cycle 10:640–647. http://dx.doi.org/10.4161/cc.10.4.14863.
   PubMed Web of Science ®Google Scholar
• Cid MC, Kleinman HK, Grant DS, Schnaper HW, Fauci AS, Hoffman GS. 1994. Estradiol enhances leukocyte binding to tumor necrosis factor (TNF)-stimulated endothelial cells via an increase in TNF-induced adhesion molecules E-selectin, intercellular adhesion molecule type 1, and vascular cell adhesion molecule type 1. J. Clin. Invest. 93:17–25. http://dx.doi.org/10.1172/JCI116941.
   PubMed Web of Science ®Google Scholar
• Munro JM, Pober JS, Cotran RS. 1989. Tumor necrosis factor and interferon-gamma induce distinct patterns of endothelial activation and associated leukocyte accumulation in skin of Papio anubis. Am. J. Pathol. 135:121–133.
   PubMed Web of Science ®Google Scholar
• Osborn L, Hession C, Tizard R, Vassallo C, Luhowskyj S, Chi-Rosso G, Lobb R. 1989. Direct expression cloning of vascular cell adhesion molecule 1, a cytokine-induced endothelial protein that binds to lymphocytes. Cell 59:1203–1211. http://dx.doi.org/10.1016/0092-8674(89)90775-7.
   PubMed Web of Science ®Google Scholar
• Bitterman KJ, Anderson RM, Cohen HY, Latorre-Esteves M, Sinclair DA. 2002. Inhibition of silencing and accelerated aging by nicotinamide, a putative negative regulator of yeast sir2 and human SIRT1. J. Biol. Chem. 277:45099–45107. http://dx.doi.org/10.1074/jbc.M205670200.
   PubMed Web of Science ®Google Scholar
• Trapp J, Meier R, Hongwiset D, Kassack MU, Sippl W, Jung M. 2007. Structure-activity studies on suramin analogues as inhibitors of NAD+-dependent histone deacetylases (sirtuins). ChemMedChem 2:1419–1431. http://dx.doi.org/10.1002/cmdc.200700003.
   PubMed Web of Science ®Google Scholar
• Finley LW, Haigis MC. 2009. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res. Rev. 8:173–188. http://dx.doi.org/10.1016/j.arr.2009.03.003.
   PubMed Web of Science ®Google Scholar
• Butow RA, Avadhani NG. 2004. Mitochondrial signaling: the retrograde response. Mol. Cell 14:1–15. http://dx.doi.org/10.1016/S1097-2765(04)00179-0.
   PubMed Web of Science ®Google Scholar
• Smedler E, Uhlen P. 2014. Frequency decoding of calcium oscillations. Biochim. Biophys. Acta 1840:964–969. http://dx.doi.org/10.1016/j.bbagen.2013.11.015.
   PubMed Web of Science ®Google Scholar
• Collins TJ, Lipp P, Berridge MJ, Bootman MD. 2001. Mitochondrial Ca(2+) uptake depends on the spatial and temporal profile of cytosolic Ca(2+) signals. J. Biol. Chem. 276:26411–26420. http://dx.doi.org/10.1074/jbc.M101101200.
   PubMedGoogle Scholar
• Maechler P, Kennedy ED, Wang H, Wollheim CB. 1998. Desensitization of mitochondrial Ca2+ and insulin secretion responses in the beta cell. J. Biol. Chem. 273:20770–20778. http://dx.doi.org/10.1074/jbc.273.33.20770.
   PubMedGoogle Scholar
• Csordas G, Hajnoczky G. 2003. Plasticity of mitochondrial calcium signaling. J. Biol. Chem. 278:42273–42282. http://dx.doi.org/10.1074/jbc.M305248200.
   PubMedGoogle Scholar
• Bell CJ, Bright NA, Rutter GA, Griffiths EJ. 2006. ATP regulation in adult rat cardiomyocytes: time-resolved decoding of rapid mitochondrial calcium spiking imaged with targeted photoproteins. J. Biol. Chem. 281:28058–28067. http://dx.doi.org/10.1074/jbc.M604540200.
   PubMed Web of Science ®Google Scholar
• Heineman FW, Balaban RS. 1993. Effects of afterload and heart rate on NAD(P)H redox state in the isolated rabbit heart. Am. J. Physiol. 264:H433–H440.
   PubMedGoogle Scholar
• Robb-Gaspers LD, Burnett P, Rutter GA, Denton RM, Rizzuto R, Thomas AP. 1998. Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO J. 17:4987–5000. http://dx.doi.org/10.1093/emboj/17.17.4987.
   PubMedGoogle Scholar
• Ying W. 2008. NAD+/NADH and NADP+/NADPH in cellular functions and cell death: regulation and biological consequences. Antioxid. Redox. Signal. 10:179–206. http://dx.doi.org/10.1089/ars.2007.1672.
   PubMed Web of Science ®Google Scholar
• McKenna MC, Waagepetersen HS, Schousboe A, Sonnewald U. 2006. Neuronal and astrocytic shuttle mechanisms for cytosolic-mitochondrial transfer of reducing equivalents: current evidence and pharmacological tools. Biochem. Pharmacol. 71:399–407. http://dx.doi.org/10.1016/j.bcp.2005.10.011.
   PubMed Web of Science ®Google Scholar
• Mracek T, Drahota Z, Houstek J. 2013. The function and the role of the mitochondrial glycerol-3-phosphate dehydrogenase in mammalian tissues. Biochim. Biophys. Acta 1827:401–410.
   PubMed Web of Science ®Google Scholar
• Ohkawa KI, Vogt MT, Farber E. 1969. Unusually high mitochondrial alpha glycerophosphate dehydrogenase activity in rat brown adipose tissue. J. Cell Biol. 41:441–449. http://dx.doi.org/10.1083/jcb.41.2.441.
   PubMedGoogle Scholar
• Sacktor B, Cochran DG. 1958. The respiratory metabolism of insect flight muscle. I. Manometric studies of oxidation and concomitant phosphorylation with sarcosomes. Arch. Biochem. Biophys. 74:266–276.
   PubMedGoogle Scholar
• Easlon E, Tsang F, Skinner C, Wang C, Lin SJ. 2008. The malate-aspartate NADH shuttle components are novel metabolic longevity regulators required for calorie restriction-mediated life span extension in yeast. Genes Dev. 22:931–944. http://dx.doi.org/10.1101/gad.1648308.
   PubMed Web of Science ®Google Scholar
• Schmidt MT, Smith BC, Jackson MD, Denu JM. 2004. Coenzyme specificity of Sir2 protein deacetylases: implications for physiological regulation. J. Biol. Chem. 279:40122–40129. http://dx.doi.org/10.1074/jbc.M407484200.
   PubMedGoogle Scholar
• Zhao S, Xu W, Jiang W, Yu W, Lin Y, Zhang T, Yao J, Zhou L, Zeng Y, Li H, Li Y, Shi J, An W, Hancock SM, He F, Qin L, Chin J, Yang P, Chen X, Lei Q, Xiong Y, Guan KL. 2010. Regulation of cellular metabolism by protein lysine acetylation. Science 327:1000–1004. http://dx.doi.org/10.1126/science.1179689.
   PubMed Web of Science ®Google Scholar
• Nemoto S, Fergusson MM, Finkel T. 2004. Nutrient availability regulates SIRT1 through a forkhead-dependent pathway. Science 306:2105–2108. http://dx.doi.org/10.1126/science.1101731.
   PubMed Web of Science ®Google Scholar
• Hayashida S, Arimoto A, Kuramoto Y, Kozako T, Honda S, Shimeno H, Soeda S. 2010. Fasting promotes the expression of SIRT1, an NAD+-dependent protein deacetylase, via activation of PPARalpha in mice. Mol. Cell. Biochem. 339:285–292. http://dx.doi.org/10.1007/s11010-010-0391-z.
   PubMed Web of Science ®Google Scholar
• Noriega LG, Feige JN, Canto C, Yamamoto H, Yu J, Herman MA, Mataki C, Kahn BB, Auwerx J. 2011. CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability. EMBO Rep. 12:1069–1076. http://dx.doi.org/10.1038/embor.2011.151.
   PubMedGoogle Scholar
• Okazaki M, Iwasaki Y, Nishiyama M, Taguchi T, Tsugita M, Nakayama S, Kambayashi M, Hashimoto K, Terada Y. 2010. PPARbeta/delta regulates the human SIRT1 gene transcription via Sp1. Endocr. J. 57:403–413. http://dx.doi.org/10.1507/endocrj.K10E-004.
   PubMedGoogle Scholar
• Zhang Q, Wang SY, Fleuriel C, Leprince D, Rocheleau JV, Piston DW, Goodman RH. 2007. Metabolic regulation of SIRT1 transcription via a HIC1:CtBP corepressor complex. Proc. Natl. Acad. Sci. U. S. A. 104:829–833. http://dx.doi.org/10.1073/pnas.0610590104.
   PubMed Web of Science ®Google Scholar
• Nisoli E, Tonello C, Cardile A, Cozzi V, Bracale R, Tedesco L, Falcone S, Valerio A, Cantoni O, Clementi E, Moncada S, Carruba MO. 2005. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science 310:314–317. http://dx.doi.org/10.1126/science.1117728.
   PubMed Web of Science ®Google Scholar
• Ota H, Eto M, Kano MR, Kahyo T, Setou M, Ogawa S, Iijima K, Akishita M, Ouchi Y. 2010. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler. Thromb. Vasc. Biol. 30:2205–2211. http://dx.doi.org/10.1161/ATVBAHA.110.210500.
   PubMed Web of Science ®Google Scholar
• Stein S, Schafer N, Breitenstein A, Besler C, Winnik S, Lohmann C, Heinrich K, Brokopp CE, Handschin C, Landmesser U, Tanner FC, Luscher TF, Matter CM. 2010. SIRT1 reduces endothelial activation without affecting vascular function in ApoE−/− mice. Aging (Albany, NY) 2:353–360.
   PubMedGoogle Scholar
• Breitenstein A, Stein S, Holy EW, Camici GG, Lohmann C, Akhmedov A, Spescha R, Elliott PJ, Westphal CH, Matter CM, Luscher TF, Tanner FC. 2011. Sirt1 inhibition promotes in vivo arterial thrombosis and tissue factor expression in stimulated cells. Cardiovasc. Res. 89:464–472. http://dx.doi.org/10.1093/cvr/cvq339.
   PubMed Web of Science ®Google Scholar
• Cheng BB, Yan ZQ, Yao QP, Shen BR, Wang JY, Gao LZ, Li YQ, Yuan HT, Qi YX, Jiang ZL. 2012. Association of SIRT1 expression with shear stress induced endothelial progenitor cell differentiation. J. Cell. Biochem. 113:3663–3671. http://dx.doi.org/10.1002/jcb.24239.
   PubMedGoogle Scholar
• Sundaresan NR, Pillai VB, Wolfgeher D, Samant S, Vasudevan P, Parekh V, Raghuraman H, Cunningham JM, Gupta M, Gupta MP. 2011. The deacetylase SIRT1 promotes membrane localization and activation of Akt and PDK1 during tumorigenesis and cardiac hypertrophy. Sci. Signal. 4:ra46. http://dx.doi.org/10.1126/scisignal.2001465.
   PubMed Web of Science ®Google Scholar
• Yeung F, Hoberg JE, Ramsey CS, Keller MD, Jones DR, Frye RA, Mayo MW. 2004. Modulation of NF-kappaB-dependent transcription and cell survival by the SIRT1 deacetylase. EMBO J. 23:2369–2380. http://dx.doi.org/10.1038/sj.emboj.7600244.
   PubMed Web of Science ®Google Scholar
• Stein S, Schafer N, Breitenstein A, Besler C, Winnik S, Lohmann C, Heinrich K, Brokopp CE, Handschin C, Landmesser U, Tanner FC, Luscher TF, Matter CM. 2010. SIRT1 reduces endothelial activation without affecting vascular function in ApoE−/− mice. Aging 2:353–360.
   PubMedGoogle Scholar
• Gracia-Sancho J, Villarreal GJr, Zhang Y, Garcia-Cardena G. 2010. Activation of SIRT1 by resveratrol induces KLF2 expression conferring an endothelial vasoprotective phenotype. Cardiovasc. Res. 85:514–519. http://dx.doi.org/10.1093/cvr/cvp337.
   PubMed Web of Science ®Google Scholar
• Csiszar A, Labinskyy N, Podlutsky A, Kaminski PM, Wolin MS, Zhang C, Mukhopadhyay P, Pacher P, Hu F, de Cabo R, Ballabh P, Ungvari Z. 2008. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am. J. Physiol. Heart Circ. Physiol. 294:H2721–H2735. http://dx.doi.org/10.1152/ajpheart.00235.2008.
   PubMed Web of Science ®Google Scholar