Cystathionine γ lyase–hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes

Cai, Junyan; Shi, Xiaoqin; Wang, Huamin; Fan, Juan; Feng, Yongliang; Lin, Xiaochen; Yang, Jichun; Cui, Qinghua; Tang, Chaoshu; Gao, Xu; Geng, Bin

doi:10.1016/j.bbalip.2016.03.001

Cited by 90 publications

(70 citation statements)

References 43 publications

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“…Recently, H 2 S was shown to directly S‐sulfhydrate PPARγ. S‐sulfhydration of PPAR γ at Cys 139 increased nuclear PPARγ accumulation, enhanced DNA binding activity to promoter of the PPARγ response element, and promoted adipogenesis gene expression in adipocytes, which were blocked by DTT or Cys 139 mutation of PPARγ (Cai et al, ). As far as we know, PPAR is a dominant factor in blood lipid and glucose metabolism.…”

Section: H2s Induced Protein S‐sulfhydrationmentioning

confidence: 99%

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Meng

Zhao

Xie

et al. 2017

British J Pharmacology

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Section: H2s Induced Protein S‐sulfhydrationmentioning

confidence: 99%

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Meng

Zhao

Xie

et al. 2017

British J Pharmacology

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“…A study revealed that endogenous H 2 S could induce mRNA and protein expression of PPAR‐ γ (Cai et al. ), indicating that exogenous H 2 S supplementation could be employed as a beneficial strategy to improve neoangiogenesis defect in HHcy patients. Hence, the purpose of our study was to answer the following questions: (i) Does HHcy inhibit neoangiogenesis via downregulation of angiogenic signals like HIF1 α and VEGF in the postfemoral artery ligation (FAL) hind limb of CBS +/− mice?…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis

et al. 2018

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Neoangiogenesis is a fundamental process which helps to meet energy requirements, tissue growth, and wound healing. Although previous studies showed that Peroxisome proliferator‐activated receptor (PPAR‐γ) regulates neoangiogenesis via upregulation of vascular endothelial growth factor (VEGF), and both VEGF and PPAR‐γ expressions were inhibited during hyperhomocysteinemic (HHcy), whether these two processes could trigger pathological effects in skeletal muscle via compromising neoangiogenesis has not been studied yet. Unfortunately, there are no treatment options available to date for ameliorating HHcy‐mediated neoangiogenic defects. Hydrogen sulfide (H2S) is a novel gasotransmitter that can induce PPAR‐γ levels. However, patients with cystathionine‐β‐synthase (CBS) mutation(s) cannot produce a sufficient amount of H2S. We hypothesized that exogenous supplementation of H2S might improve HHcy‐mediated poor neoangiogenesis via the PPAR‐γ/VEGF axis. To examine this, we created a hind limb femoral artery ligation (FAL) in CBS +/− mouse model and treated them with GYY4137 (a long‐acting H2S donor compound) for 21 days. To evaluate neoangiogenesis, we used barium sulfate angiography and laser Doppler blood flow measurements in the ischemic hind limbs of experimental mice post‐FAL to assess blood flow. Proteins and mRNAs levels were studied by Western blots and qPCR analyses. HIF1‐α, VEGF, PPAR‐γ and p‐eNOS expressions were attenuated in skeletal muscle of CBS +/− mice after 21 days of FAL in comparison to wild‐type (WT) mice, that were improved via GYY4137 treatment. We also found that the collateral vessel density and blood flow were significantly reduced in post‐FAL CBS +/− mice compared to WT mice and these effects were ameliorated by GYY4137. Moreover, we found that plasma nitrite levels were decreased in post‐FAL CBS +/− mice compared to WT mice, which were mitigated by GYY4137 supplementation. These results suggest that HHcy can inhibit neoangiogenesis via antagonizing the angiogenic signal pathways encompassing PPAR‐γ/VEGF axis and that GYY4137 could serve as a potential therapeutic to alleviate the harmful metabolic effects of HHcy conditions.

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“…Over the past decade, this molecule has been shown to be synthesised by a range of tissues in which it functions as a signalling molecule with distinct physiological and biochemical effects [1–3]. To date, the spectrum of signalling systems identified include, but is not restricted to, nuclear factor-kappa beta (NF-κB), the activity of several kinases, including p38 mitogen-activated protein kinase (p38 MAPK) [4], c-JunNH 2 -terminal kinase (JNK) [5], extracellular signal-regulated kinase (ERK) [6], phosphoinositide 3-kinase-protein kinase B (PI-3K-Akt) [7], protein kinase C (PKC) [8], nuclear factor erythroid 2-related factor 2 (Nrf-2) [9], p53 [10], AMP-activated protein kinase [11], proliferator-activated receptor γ [12], NAD-dependent deacetylase sirtuin-1 (SIRT1) [13], SIRT3 [14], and mechanistic target of rapamycin (mTOR) [15]. Studies focused on delineating these molecular networks have revealed H 2 S to have important roles in cytoprotection [16–20], inflammation [21–24], vascular function [25–27], neurological systems [28], tissue repair and healing [29–34], apoptosis and the cell cycle [35, 36], mitochondrial function and energy metabolism and biogenesis [37–48], obesity [49–53], and in ageing [54–60].…”

Section: Introductionmentioning

confidence: 99%

H2S biosynthesis and catabolism: new insights from molecular studies

Rose

Moore

Zhu

2016

Cell. Mol. Life Sci.

139

100

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Hydrogen sulfide (H2S) has profound biological effects within living organisms and is now increasingly being considered alongside other gaseous signalling molecules, such as nitric oxide (NO) and carbon monoxide (CO). Conventional use of pharmacological and molecular approaches has spawned a rapidly growing research field that has identified H2S as playing a functional role in cell-signalling and post-translational modifications. Recently, a number of laboratories have reported the use of siRNA methodologies and genetic mouse models to mimic the loss of function of genes involved in the biosynthesis and degradation of H2S within tissues. Studies utilising these systems are revealing new insights into the biology of H2S within the cardiovascular system, inflammatory disease, and in cell signalling. In light of this work, the current review will describe recent advances in H2S research made possible by the use of molecular approaches and genetic mouse models with perturbed capacities to generate or detoxify physiological levels of H2S gas within tissues.

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Cystathionine γ lyase–hydrogen sulfide increases peroxisome proliferator-activated receptor γ activity by sulfhydration at C139 site thereby promoting glucose uptake and lipid storage in adipocytes

Cited by 90 publications

References 43 publications

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Protein S‐sulfhydration by hydrogen sulfide in cardiovascular system

Hydrogen sulfide improves postischemic neoangiogenesis in the hind limb of cystathionine-β-synthase mutant mice via PPAR-γ/VEGF axis

H2S biosynthesis and catabolism: new insights from molecular studies

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