Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti‐aging and metabolic effects of sirtuins

Law, Ivy Ka Man; Liu, Ling; Xu, Aimin; Lam, Karen S.L.; Vanhoutte, Paul M.; Che, Chi‐Ming; Leung, Priscilla T.Y.; Wang, Yudong

doi:10.1002/pmic.200800738

Cited by 102 publications

(88 citation statements)

References 72 publications

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“…More recent studies have shown that SIRT3 deacetylates the succinate dehydrogenase flavoprotein subunit and increases complex II activity (Cimen et al, 2010). SIRT3 was also shown to directly bind and possibly deacetylate ATP5a (Law et al, 2009), a subunit of complex V. This evidence further supports a role for SIRT3 in regulating energy metabolism, which could provide beneficial effects during ischemic episodes.…”

Section: Roles Of Mitochondrial Sirtuins In Mitochondrial Metabolismsupporting

confidence: 51%

Pathways for Ischemic Cytoprotection: Role of Sirtuins in Caloric Restriction, Resveratrol, and Ischemic Preconditioning

Morris

Lin

Thompson

et al. 2011

J Cereb Blood Flow Metab

120

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Caloric restriction (CR), resveratrol, and ischemic preconditioning (IPC) have been shown to promote protection against ischemic injury in the heart and brain, as well as in other tissues. The activity of sirtuins, which are enzymes that modulate diverse biologic processes, seems to be vital in the ability of these therapeutic modalities to prevent against cellular dysfunction and death. The protective mechanisms of the yeast Sir2 and the mammalian homolog sirtuin 1 have been extensively studied, but the involvement of other sirtuins in ischemic protection is not yet clear. We examine the roles of mammalian sirtuins in modulating protective pathways against oxidative stress, energy depletion, excitotoxicity, inflammation, DNA damage, and apoptosis. Although many of these sirtuins have not been directly implicated in ischemic protection, they may have unique roles in enhancing function and preventing against stress-mediated cellular damage and death. This review will include in-depth analyses of the roles of CR, resveratrol, and IPC in activating sirtuins and in mediating protection against ischemic damage in the heart and brain.

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Section: Roles Of Mitochondrial Sirtuins In Mitochondrial Metabolismsupporting

confidence: 51%

Pathways for Ischemic Cytoprotection: Role of Sirtuins in Caloric Restriction, Resveratrol, and Ischemic Preconditioning

Morris

Lin

Thompson

et al. 2011

J Cereb Blood Flow Metab

120

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“…Specifically, deacetylation regulates the activity of IDH (Schlicker et al, 2008), cytochrome c reductase (Ahn et al, 2008) and MDH ; three enzymes we identified in M. trossulus together with sirtuin 5. A recent study identified a number of proteins interacting with sirtuins (Law et al, 2009), including several Hsp70s and MAPK/Erk; again, these are proteins we found responding to acute heat stress in Mytilus. In addition, a reduction in MAPK/Erk is generally associated with reduced cell survival (Nadeau and Landry, 2007), an observation consistent with our results in M. trossulus and the reduction of the sirtuin 5 isoform (Figs3 and 10).…”

Section: Hypotheses Integrating the Observed Heat-stress-induced Chanmentioning

confidence: 96%

The proteomic response of the mussel congenersMytilus galloprovincialisandM. trossulusto acute heat stress: implications for thermal tolerance limits and metabolic costs of thermal stress

Tomanek

Zuzow

2010

Journal of Experimental Biology

272

273

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SUMMARYThe Mediterranean blue mussel, Mytilus galloprovincialis, an invasive species in California, has displaced the more heat-sensitive native congener, Mytilus trossulus, from its former southern range, possibly due to climate change. By comparing the response of their proteomes to acute heat stress we sought to identify responses common to both species as well as differences that account for greater heat tolerance in the invasive. Mussels were acclimated to 13°C for four weeks and exposed to acute heat stress (24°C, 28°C and 32°C) for 1h and returned to 13°C to recover for 24h. Using two-dimensional gel electrophoresis and tandem mass spectrometry we identified 47 and 61 distinct proteins that changed abundance in M. galloprovincialis and M. trossulus, respectively. The onset temperatures of greater abundance of some members of the heat shock protein (Hsp) 70 and small Hsp families were lower in M. trossulus. The abundance of proteasome subunits was lower in M. galloprovincialis but greater in M. trossulus in response to heat. Levels of several NADH-metabolizing proteins, possibly linked to the generation of reactive oxygen species (ROS), were lower at 32°C in the cold-adapted M. trossulus whereas proteins generating NADPH, important in ROS defense, were higher in both species. The abundance of oxidative stress proteins was lower at 32°C in M. trossulus only, indicating that its ability to combat heat-induced oxidative stress is limited to lower temperatures. Levels of NADdependent deacetylase (sirtuin 5), which are correlated with lifespan, were lower in M. trossulus in response to heat stress. In summary, the expression patterns of proteins involved in molecular chaperoning, proteolysis, energy metabolism, oxidative damage, cytoskeleton and deacetylation revealed a common loci of heat stress in both mussels but also showed a lower sensitivity to high-temperature damage in the warm-adapted M. galloprovincialis, which is consistent with its expanding range in warmer waters. Supplementary material available online at

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“…In addition, vectors encoding glutathione S-transferase (GST)-tagged SIRT1 mutants (GST-hSIRT1-S47A and GSThSIRT1-S47D) were constructed by use of the template plasmid GST-hSIRT1-WT. 30 All mutations were confirmed by DNA sequencing.…”

Section: Site-directed Mutagenesismentioning

confidence: 99%

Cyclin-Dependent Kinase 5–Mediated Hyperphosphorylation of Sirtuin-1 Contributes to the Development of Endothelial Senescence and Atherosclerosis

Bai

Liang

et al. 2012

Circulation

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Background-Endothelial senescence represents one of the major characteristics of vascular aging and promotes the development of atherosclerosis. Sirtuin-1 (SIRT1) is an NAD-dependent deacetylase possessing antiaging activities. During the occurrence of endothelial senescence, both the expression and activity of SIRT1 are downregulated. The present study was designed to investigate the molecular mechanisms contributing to the loss-of-SIRT1 function in senescent endothelial cells. Methods and Results-After repetitive passages, primary cultures of porcine aortic endothelial cells exhibited a severe senescence phenotype. Western blotting revealed that phosphorylation of SIRT1 at serine 47 (S47) was significantly enhanced in senescent endothelial cells. S47 phosphorylation was stimulated by agents promoting senescence and attenuated by drugs with antisenescence properties. Mutation of S47 to nonphosphorable alanine (S47A) enhanced whereas replacing S47 with phospho-mimicking aspartic acid (S47D) abolished the antisenescent, growth-promoting, and LKB1-downregulating actions of SIRT1. Phosphorylation at S47 was critically involved in the nuclear retention of SIRT1 but abolished its association with the telomeric repeat-binding factor 2-interacting protein 1. Cyclin-dependent kinase 5 (CDK5) was identified as an SIRT1 kinase modulating S47 phosphorylation. Knockdown or inhibition of CDK5 reduced the number of senescent endothelial cells, promoted nuclear exportation of SIRT1, and attenuated the expression of inflammatory genes in porcine aortic endothelial cells. The truncated regulatory subunit of CDK5, P25, accumulated in senescent porcine aortic endothelial cells and atherosclerotic aortas. Long-term treatment with roscovitine, a CDK5 inhibitor, blocked the development of cellular senescence and atherosclerosis in aortas of hypercholesterolemic apolipoprotein E-deficient mice. Conclusion-CDK5-mediated

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Identification and characterization of proteins interacting with SIRT1 and SIRT3: implications in the anti‐aging and metabolic effects of sirtuins

Cited by 102 publications

References 72 publications

Pathways for Ischemic Cytoprotection: Role of Sirtuins in Caloric Restriction, Resveratrol, and Ischemic Preconditioning

Pathways for Ischemic Cytoprotection: Role of Sirtuins in Caloric Restriction, Resveratrol, and Ischemic Preconditioning

The proteomic response of the mussel congenersMytilus galloprovincialisandM. trossulusto acute heat stress: implications for thermal tolerance limits and metabolic costs of thermal stress

Cyclin-Dependent Kinase 5–Mediated Hyperphosphorylation of Sirtuin-1 Contributes to the Development of Endothelial Senescence and Atherosclerosis

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