Molecular and Cellular Characterization of SIRT1 Allosteric Activators

Schultz, Michael; Rinaldi, Conrad; Lu, Yuancheng; Amorim, João A.; Sinclair, David A.

doi:10.1007/978-1-4939-9434-2_8

Cited by 11 publications

(3 citation statements)

References 28 publications

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“…In addition to SIRT1, resveratrol has been reported to activate SIRT3 and SIRT5, as well as other non-sirtuin targets [ 10 ]. After that, several generations of STACs with increasing potency and specificity are generated, including SRT1720 and SRT2104 [ 150 ]. STACs bind to the STAC-binding domain in the N terminus of SIRT1 and increase the binding affinity of a substrate for SIRT1 [ 151 ].…”

Section: Discussionmentioning

confidence: 99%

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

et al. 2020

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Ischemia/reperfusion (I/R) injury is the central cause of global death in cardiovascular diseases, which is characterized by disorders such as angina, stroke, and peripheral vascular disease, finally causing severe debilitating diseases and death. The increased rates of morbidity and mortality caused by I/R are parallel with aging. Aging-associated cardiac physiological structural and functional deterioration were found to contribute to abnormal reactive oxygen species (ROS) production during I/R stress. Disturbed redox homeostasis could further trigger the related signaling pathways that lead to cardiac irreversible damages with mitochondria dysfunction and cell death. It is notable that sirtuin proteins are impaired in aged hearts and are critical to maintaining redox homeostasis via regulating substrate metabolism and inflammation and thus preserving cardiac function under stress. This review discussed the cellular and functional alterations upon I/R especially in aging hearts. We propose that mitochondria are the primary source of reactive oxygen species (ROS) that contribute to I/R injury in aged hearts. Then, we highlight the cardiomyocyte protection of the age-related proteins Sirtuin1 (SIRT1) and Sirtuin1 (SIRT3) in response to I/R injury, and we discuss their modulation of cardiac metabolism and the inflammatory reaction that is involved in ROS formation.

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Section: Discussionmentioning

confidence: 99%

SIRT1/SIRT3 Modulates Redox Homeostasis during Ischemia/Reperfusion in the Aging Heart

et al. 2020

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“…A previous publication extensively studied the functional relationship between SIRT1 and EDN2 [53]. It indicated that activating SIRT1 via discrete mechanisms, namely, by SRT2104, resveratrol, and metformin [75, 89, 94, 95], each inhibited EDN2 expression, reinforcing the conclusion that enhanced SIRT1 activity downregulates EDN2 transcripts in hGLCs. Further evidence was provided through an siRNA silencing approach; knockdown of SIRT1 in SVOG cells resulted in the time-dependent elevation of EDN2 expression and prevented the inhibition induced by the SIRT1 activator, SRT2104.…”

Section: Introductionmentioning

confidence: 86%

Divergent roles of sirtuin 1 in human granulosa-lutein cells: similarities to human chorionic gonadotropin

Meidan

Szymańska

2023

Biology of Reproduction

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Sirtuin 1 (SIRT1) is an NAD+ dependent deacetylase that modifies gene expression through histone deacetylation. It also deacetylates non-histone substrates, e.g. tumor suppressor p53, NOS3, HIF1A, NFKB, FOXO3a, PGC-1α, and PPARγ. Consequently, it regulates a wide range of physiological functions including cell cycle control, energy expenditure, oxidative stress response, apoptosis, and aging. SIRT1 is expressed in ovarian granulosa cells (GCs) of various species including humans at different stages of the reproductive cycle. The importance of SIRT1 in female reproduction is supported by the findings that SIRT1-knockout mice exhibit defects in reproductive tissue development. These mice were found to have a thin-walled uterus, small ovaries, with follicles present but no corpora lutea. This review aims to provide state-of-the-art information on SIRT1’s mode of action and its roles in human granulosa-lutein cells and GCs from other species where data is available. It also discusses the overlapping actions of SIRT1 and hCG on the production of critical GC-borne factors.

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“…Resveratrol, a flavanol found naturally in peanuts, mulberries, raspberries, blueberries and grapes, inhibits class I, II, and IV HDACs in a dose-dependent manner [ 109 ], but has opposite effects on class III HDACs, serving as an allosteric sirtuin activating compound [ 110 ]. Thus, resveratrol regulates several signal transduction pathways involved in cancer, aging, inflammation, and neurodegeneration.…”

Section: Flavonoidsmentioning

confidence: 99%