Sirtuin 6 protects the heart from hypoxic damage

Maksin-Matveev, Anna; Kanfi, Yariv; Hochhauser, Edith; Isak, Ahuva; Cohen, Haim Y.; Shainberg, Asher

doi:10.1016/j.yexcr.2014.07.013

Cited by 84 publications

(59 citation statements)

References 40 publications

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“…They were first discovered in yeast as a transcriptional repressor called silent information regulator 2 protein (Sir2) (Klar et al , 1979; Rine and Herskowitz, 1987). All eukaryotes encode sirtuins in their genomes as sirtuins have important functions in regulating cellular stress responses (Brunet et al , 2004; Dai et al , 2014; Maksin-Matveev et al , 2015), mitochondrial biogenesis (Brenmoehl and Hoeflich, 2013), apoptosis (Alcendor et al , 2004; Motta et al , 2004), metabolism (Purushotham et al , 2009), fatty acid oxidation (Hirschey et al , 2010), and inflammation (Cao et al , 2013; Liu and McCall, 2013). …”

Section: Pharmacologic Therapiesmentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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Mitochondria are a major target in hypoxic/ischemic injury. Mitochondrial impairment increases with age leading to dysregulation of molecular pathways linked to mitochondria. The perturbation of mitochondrial homeostasis and cellular energetics worsens outcome following hypoxic-ischemic insults in elderly individuals. In response to acute injury conditions, cellular machinery relies on rapid adaptations by modulating posttranslational modifications. Therefore, post-translational regulation of molecular mediators such as hypoxia-inducible factor 1α (HIF-1α), peroxisome proliferator-activated receptor γ coactivator α (PGC-1α), c-MYC, SIRT1 and AMPK play a critical role in the control of the glycolytic-mitochondrial energy axis in response to hypoxic-ischemic conditions. The deficiency of oxygen and nutrients leads to decreased energetic reliance on mitochondria, promoting glycolysis. The combination of pseudohypoxia, declining autophagy, and dysregulation of stress responses with aging adds to impaired host response to hypoxic-ischemic injury. Furthermore, intermitochondrial signal propagation and tissue wide oscillations in mitochondrial metabolism in response to oxidative stress are emerging as vital to cellular energetics. Recently reported intercellular transport of mitochondria through tunneling nanotubes also play a role in the response to and treatments for ischemic injury. In this review we attempt to provide an overview of some of the molecular mechanisms and potential therapies involved in the alteration of cellular energetics with aging and injury with a neurobiological perspective.

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Section: Pharmacologic Therapiesmentioning

confidence: 99%

Mitochondrial function in hypoxic ischemic injury and influence of aging

Ham

Raju

2017

Progress in Neurobiology

282

205

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“…Thus, SIRT6 prevents cells from premature senescence 70 . Sirt6 null mice show the premature aging phenotype whereas male, but not female, global Sirt6 over-expressing mice show a longer lifespan with cardioprotection against hypoxia 5, 6, 70, 71 . Endothelial cells highly express SIRT6 and deficiency of endothelial SIRT6 accelerates replicative senescence 72 .…”

Section: Roles Of Sirt Proteins In Vascular Agingmentioning

confidence: 99%

Sirtuins, Cell Senescence, and Vascular Aging

Kida

Goligorsky

2016

Canadian Journal of Cardiology

225

161

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The sirtuin (SIRTs) constitute a class of proteins with NAD+-dependent deacetylase or ADP-ribosyltransferase activity. Seven SIRT family members have been identified in mammals, from SIRT1, the best studied for its role in vascular aging, to SIRT7. SIRT1 and SIRT2 are localized both in the nucleus and cytoplasm. SIRT3, SIRT4, and SIRT5 are mitochondrial, while SIRT6 and SIRT7 are nuclear. Extensive studies have clearly revealed that SIRT proteins regulate diverse cell functions and responses to stressors. Vascular aging involves the aging process (senescence) of endothelial and vascular smooth muscle cells. Two types of cell senescence have been identified: (1) replicative senescence with telomere attrition and (2) stress-induced premature senescence without telomere involvement. Both types of senescence induce vascular cell growth arrest and loss of vascular homeostasis, contributing to the initiation and progression of cardiovascular diseases. Previous mechanistic studies have revealed in detail that SIRT1, SIRT3, and SIRT6 demonstrate protective functions against vascular aging, while definite vascular function of other SIRTs is under investigation. Thus, direct SIRT modulation and NAD+ stimulation of SIRT are promising candidates for cardiovascular disease therapy. A small number of pilot studies have been conducted to assess SIRT modulation in humans. These clinical studies have not yet provided convincing evidence that SIRT proteins alleviate morbidity and mortality in patients with cardiovascular diseases. The outcomes of multiple ongoing clinical trials are awaited to define the efficacy of SIRT modulators and SIRT activators in cardiovascular diseases, along with the potential adverse effects of chronic SIRT modulation.

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“…Moreover, SIRT6 modulated cholesterol and fatty acid metabolism, by regulating SREBP-1 target genes implicated in fatty acid production such as acetyl-CoA carboxylase 1 (ACC1), and stearoyl-CoA desaturase 1 (SCD1) [156,158–160]. Other protective mechanisms of SIRT6 have been also well studied, including the regulation of AMPKα pathway, B-cell lymphoma 2 (Bcl2), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), and Akt pathway during metabolic stress [161]. SIRT7 has been reported to regulate lipid metabolism, fatty acid uptake and synthesis/storage of triglycerides, probably by targeting nuclear receptor testicular receptor 4/transforming growth factor-(β-activated kinase (TR4/TAK1) [162].…”

Section: Sirtuin-mediated Deacetylation In Metabolismmentioning

confidence: 99%

MicroRNAs in heart failure: Non-coding regulators of metabolic function

Schulze

2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Heart failure (HF) is the inability of the heart to provide sufficient cardiac output for the energy demands of the body. Over the last decades, our understanding of the role of microRNAs (miRNAs), a class of small non-coding RNA regulators of gene expression at the post-transcriptional level, in cardiovascular diseases has expanded at a rapid rate. Importantly, multiple miRNAs have been specifically implicated in the progression of HF. Growing evidence suggests that miRNAs regulate central metabolic pathways and thus are highly implicated in the maintenance of energy homeostasis. In this review, we highlight recent discoveries of the mechanistic role of miRNAs in regulating metabolic functions in HF, with specific focus on the implication of miRNAs in metabolic rearrangements, discuss the potential value of miRNA profiles as novel HF biomarkers, and summarize the recent investigations on therapeutic approaches using miRNAs in heart disease. This article is part of a Special Issue entitled: The role of post-translational protein modifications on heart and vascular metabolism edited by Jason R.B. Dyck & Jan F.C. Glatz.

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Sirtuin 6 protects the heart from hypoxic damage

Cited by 84 publications

References 40 publications

Mitochondrial function in hypoxic ischemic injury and influence of aging

Mitochondrial function in hypoxic ischemic injury and influence of aging

Sirtuins, Cell Senescence, and Vascular Aging

MicroRNAs in heart failure: Non-coding regulators of metabolic function

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