Catalytic-independent neuroprotection by SIRT1 is mediated through interaction with HDAC1.

08:00 EDT 11th April 2019 | BioPortfolio

Summary of "Catalytic-independent neuroprotection by SIRT1 is mediated through interaction with HDAC1."

SIRT1, a NAD+-dependent deacetylase, protects neurons in a variety of in vitro and in vivo models of neurodegenerative disease. We have previously described a neuroprotective effect by SIRT1 independent of its catalytic activity. To confirm this conclusion we tested a panel of SIRT1 deletion mutant constructs, designated Δ1-Δ10, in cerebellar granule neurons induced to undergo apoptosis by low potassium treatment. We find that deletions of its N-terminal, those lacking portions of the catalytic domain, as well as one that lacks the ESA (Essential for SIRT1 Activity) motif, are as protective as wild-type SIRT1. In contrast, deletion of the region spanning residues 542-609, construct Δ8, substantially reduced the neuroprotective activity of SIRT1. As observed with LK-induced apoptosis, all SIRT1 constructs except Δ8 protect neurons against mutant huntingtin toxicity. Although its own catalytic activity is not required, neuroprotection by SIRT1 is abolished by inhibitors of Class I HDACs as well as by knockdown of endogenous HDAC1. We find that SIRT1 interacts with HDAC1 and this interaction is greatly increased by deleting regions of SIRT1 necessary for its catalytic activity. However, SIRT1-mediated protection is not dependent on HDAC1 deacetylase activity. Although other studies have described that catalytic activity of SIRT1 mediates is neuroprotective effect, our study suggests that in cerebellar granule neurons its deacetylase activity is not important and that HDAC1 contributes to the neuroprotective effect of SIRT1.


Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0215208


DeepDyve research library

PubMed Articles [14750 Associated PubMed Articles listed on BioPortfolio]

Histone Deacetylase SIRT1 Targets Plk2 to Regulate Centriole Duplication.

The protein deacetylase SIRT1 (Sirtuin 1) regulates many cellular processes, including cell-cycle progression, DNA damage response, and metabolism. Although the centrosome is a key regulator of cell-c...

HSF1/HSP pathway in the hippocampus is involved in SIRT1-mediated caloric restriction-induced neuroprotection after surgery in aged mice.

Postoperative cognitive dysfunction is common in the elderly. Endoplasmic reticulum stress (ER-stress) increases neuronal apoptosis after surgery, and chaperone molecules, such as heat shock proteins ...

Assessing the performance of three resveratrol in binding with SIRT1 by molecular dynamics simulation and MM/GBSA methods: the weakest binding of resveratrol 3 to SIRT1 triggers a possibility of dissociation from its binding site.

SIRT1 is an NAD+-dependent deacetylase, whose activators have potential therapeutic applications in the age-related, metabolic, neurode-generative and cardiovascular diseases. Resveratrol (RSV) has be...

Melatonin protective effect against amyloid β-induced neurotoxicity mediated by mitochondrial biogenesis; involvement of hippocampal Sirtuin-1 signaling pathway.

Melatonin has a potential therapeutic value in Alzheimer's disease (AD), a disease that is associated with a dramatic decline in memory and cognitive abilities. The aggregation of the amyloid β (Aβ)...

Metformin and tenovin-6 synergistically induces apoptosis through LKB1-independent SIRT1 down-regulation in non-small cell lung cancer cells.

Sirtuin 1 (SIRT1) is known to play a role in a variety of tumorigenesis processes by deacetylating histone and non-histone proteins; however, antitumour effects by suppressing SIRT1 activity in non-sm...

Clinical Trials [2975 Associated Clinical Trials listed on BioPortfolio]

Sirtuin Mediated Effects of 36 Hour Fast and 1 Hour Exercise

Hypothesis: during fasting and exercise will there be an activation of sirtuins (Sirt1). Primarily the investigators will investigate Sirt1 activity in muscle- and fat-biopsies after fast...

Dried Fruit and Postprandial Glycemia Trial

Dried fruits show promising potential for the management of blood glucose. Previous trials have reported beneficial effects of raisins on post-prandial glucose and insulin responses in hea...

Meta-analyses of the Effect of 'Catalytic' Doses of Fructose and Its Epimers on Carbohydrate Metabolism

Despite advances in the prevention and treatment of type 2 diabetes, its prevalence continues to rise worldwide. There is a need for new modalities to improve metabolic control in individu...

Vitamin D Supplementation And Varicella Zoster Virus Vaccine Responsiveness In Older Long-Term Care Residents

Objectives 1. To determine the increase in VZV-specific cell-mediated immune response from pre-zoster vaccination to 3 weeks post-vaccination in nursing home residents after 4 mont...

Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? (ATRU-4).

Purpose: The overall hypothesis of the study is that the benefits attained in the EMPA-OUTCOME were, at least in part, mediated by a glucose-independent mechanism. Thus, to demonstrate th...

Medical and Biotech [MESH] Definitions

A catalytic subunit of the NuA4 histone acetyltransferase complex that functions in transcriptional activation of genes by acetylation of nucleosomal HISTONES H4 and H2A, altering nucleosome-DNA interactions and interaction of the modified histones with other activating transcription factors. It may control gene expression changes associated with oncogene and proto-oncogene mediated growth induction, tumor suppressor mediated growth arrest; CELL AGING; APOPTOSIS; and DNA REPAIR. It is polyubiquitinated and degraded during HIV-1 infection through its interaction with the viral TAT PROTEIN.

RNA that has catalytic activity. The catalytic RNA sequence folds to form a complex surface that can function as an enzyme in reactions with itself and other molecules. It may function even in the absence of protein. There are numerous examples of RNA species that are acted upon by catalytic RNA, however the scope of this enzyme class is not limited to a particular type of substrate.

Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.

Cell surface receptors for obesity factor (LEPTIN), a hormone secreted by the WHITE ADIPOCYTES. Upon leptin-receptor interaction, the signal is mediated through the JAK2/STAT3 pathway to regulate food intake, energy balance and fat storage.

A synuclein that is a major component of LEWY BODIES that plays a role in neurodegeneration and neuroprotection.

Quick Search


DeepDyve research library

Searches Linking to this Article