SIRT1 Interacts with and Deacetylates ATP6V1B2 in Mature Adipocytes

Kim, Sun-Yee; Zhang, Qiongyi; Brunmeir, Reinhard; Han, Weiping; Xu, Feng

doi:10.1371/journal.pone.0133448

Cited by 8 publications

(5 citation statements)

References 37 publications

(46 reference statements)

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“…Finally, to examine whether our pan-acetyl-lysine antibodies could actually pull-down acetylated proteins from the whole cell lysates, we performed immunoprecipitation assay [ 15 ] using either a control rabbit IgG or our antibodies SICS38 to SICS42. As shown in S4 Fig , all five SICS antibodies could immunoprecipitate significant amount of acetylated proteins from the whole cell lysates of TSA and NAM treated HEK293 cells as detected by immunoblotting.…”

Section: Resultsmentioning

confidence: 99%

“…HEK293 cells treated with TSA and NAM were lysed in RIPA lysis buffer (50 mM Tris-HCl [pH = 7.4], 150 mM NaCl, 0.1% SDS, 0.25% Na-deoxycholate, 1% NP-40) containing protease inhibitor cocktail (Roche). Immunoprecipitation was performed using either a control rabbit IgG or SICS antisera from #38 to #42 as described previously [ 15 ]. The immunoprecipitated proteins were then immunoblotted with a mouse pan-acetyl-lysine antibody (#9681, Cell Signaling).…”

Section: Methodsmentioning

confidence: 99%

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An Alternative Strategy for Pan-acetyl-lysine Antibody Generation

et al. 2016

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Lysine acetylation is an important post-translational modification in cell signaling. In acetylome studies, a high-quality pan-acetyl-lysine antibody is key to successful enrichment of acetylated peptides for subsequent mass spectrometry analysis. Here we show an alternative method to generate polyclonal pan-acetyl-lysine antibodies using a synthesized random library of acetylated peptides as the antigen. Our antibodies are tested to be specific for acetyl-lysine peptides/proteins via ELISA and dot blot. When pooled, five of our antibodies show broad reactivity to acetyl-lysine peptides, complementing a commercial antibody in terms of peptide coverage. The consensus sequence of peptides bound by our antibody cocktail differs slightly from that of the commercial antibody. Lastly, our antibodies are tested in a proof-of-concept to analyze the acetylome of HEK293 cells. In total we identified 1557 acetylated peptides from 416 proteins. We thus demonstrated that our antibodies are well-qualified for acetylome studies and can complement existing commercial antibodies.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

An Alternative Strategy for Pan-acetyl-lysine Antibody Generation

et al. 2016

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“…One of the HDAC class enzymes, SIRT1 (silent inflammation regulator 1), is known to play role in inflammation, aging, cell senescence, and emphysema formation in COPD [ 103 ]. Ma et al demonstrated that upregulated SIRT1 expression controlled NF-κB acetylation and repressed inflammatory responses through erythromycin [ 104 ].…”

Section: Epigenetic Dysregulation In Ipf and Copdmentioning

confidence: 99%

Epigenetic Mechanisms in Parenchymal Lung Diseases: Bystanders or Therapeutic Targets?

Avci

Sarvari

Savai

et al. 2022

IJMS

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Epigenetic responses due to environmental changes alter chromatin structure, which in turn modifies the phenotype, gene expression profile, and activity of each cell type that has a role in the pathophysiology of a disease. Pulmonary diseases are one of the major causes of death in the world, including lung cancer, idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), pulmonary hypertension (PH), lung tuberculosis, pulmonary embolism, and asthma. Several lines of evidence indicate that epigenetic modifications may be one of the main factors to explain the increasing incidence and prevalence of lung diseases including IPF and COPD. Interestingly, isolated fibroblasts and smooth muscle cells from patients with pulmonary diseases such as IPF and PH that were cultured ex vivo maintained the disease phenotype. The cells often show a hyper-proliferative, apoptosis-resistant phenotype with increased expression of extracellular matrix (ECM) and activated focal adhesions suggesting the presence of an epigenetically imprinted phenotype. Moreover, many abnormalities observed in molecular processes in IPF patients are shown to be epigenetically regulated, such as innate immunity, cellular senescence, and apoptotic cell death. DNA methylation, histone modification, and microRNA regulation constitute the most common epigenetic modification mechanisms.

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“…However, as a NAD + precursor it is expected to improve lysosomal function in view of the following molecular mechanisms: mitochondrial dysfunction leads to a reduction in the NAD + /NADH ratio; - NAD + precursors have shown beneficial effects in several mouse models characterized by reduced NAD + /NADH ratios [ 6 ]. This includes a marked improvement of the respiratory chain defect and exercise intolerance in a mouse model of mitochondrial disease [ 24 ]; - NAD + dependent activation of Sirtuin1 is mechanistically involved in this improvement of the phenotype [ 24 ]; - Sirtuin1 is regulating the activity of vacuolar-ATPase, needed for lysosomal acidification [ 25 , 26 ]; - NAD + is needed for correcting lysosomal acidification lost by mitochondrial translation dysfunction [ 27 ], - loss of lysosomal acidification was shown to trap iron and cobalamin [ 16 , 23 ]; – also in patients with NAD + deficiency mitochondrial function improves substantially after niacin administration [ 13 ].…”

Section: Treatment May Already Be Availablementioning

confidence: 99%

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

et al. 2021

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Iron deficiency is known to aggravate the prognosis of patients with heart failure. Iron has functions in the mitochondrial respiratory chain. In patients with reduced mitochondrial respiration, the mitochondrial ratio between the level of nicotinamide adenine dinucleotide and its reduced form decreases. Due to the mitochondrial-lysosomal interplay, decreased mitochondrial respiration also leads to inhibition of lysosomal hydrolysis. As a result, cobalamin and iron will be trapped in lysosomes. This will, even if iron and cobalamin have been consumed and absorbed in sufficient amounts, lead to their functional deficiencies. 1 Functional iron deficiency can further impede mitochondrial respiration. Increased plasma levels of methylmalonic acid were shown to predict all-cause and cardiovascular mortality in the general population. Treatments targeting mitochondrial and lysosomal function may correct the functional deficiencies and improve prognosis in a subgroup of patients with heart failure, notably those with skeletal muscle wasting. Methylmalonic acid levels may be used for monitoring response to treatment, thereby identifying patients of the subgroup in which disease outcome may improve.

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SIRT1 Interacts with and Deacetylates ATP6V1B2 in Mature Adipocytes

Cited by 8 publications

References 37 publications

An Alternative Strategy for Pan-acetyl-lysine Antibody Generation

An Alternative Strategy for Pan-acetyl-lysine Antibody Generation

Epigenetic Mechanisms in Parenchymal Lung Diseases: Bystanders or Therapeutic Targets?

The marker of cobalamin deficiency, plasma methylmalonic acid, may help identifying lysosomal iron trapping in patients. Its possible utility for heart failure

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