Selective expression of Kir6.1 protein in different vascular and non-vascular tissues

Sun, Xianfeng; Cao, Kun; Yang, Guangdong; Huang, Yu-Hung; Hanna, Salma Toma; Wang, Rui

doi:10.1016/j.bcp.2003.08.041

Cited by 31 publications

(19 citation statements)

References 24 publications

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“…Gene targeting approaches confirm an important role for these subunits in the respective tissues because Kir6.2(Ϫ/Ϫ) mice lack functional sarcolemmal K ATP channels and both Kir6.1(Ϫ/Ϫ) and SUR2(Ϫ/Ϫ) mice develop coronary abnormalities (2,17). However, these results do not explain the presence of Kir6.1 or SUR1 in cardiac myocytes (17,19,32) or the observation that anti-SUR1 antisense oligonucleotides inhibit K ATP channels of ventricular myocytes (41). Thus the molecular composition of K ATP channels and the functional roles of the individual subunits may therefore not be as clearcut as previously thought.…”

contrasting

confidence: 49%

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Tong

Porter²,

Liu³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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contrasting

confidence: 49%

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Tong

Porter²,

Liu³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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“…The supernatants containing crude cellular proteins were resolved on a 10% SDS-PAGE gel, and transferred onto the PVDC nitrocellulose membrane. 24 The membrane was blocked with 3% nonfat dry milk solution in PBS at room temperature for 2 h and rinsed three times with PBS before incubating firstly with primary antibody (1:500 for CSE antibody, 1:5000 for b-actin antibody) and then with the HRP-conjugated secondary antibody (1:5000). The immunoreactions were visualized by ECL and exposed to X-ray film (Kodak Scientific Imaging film, X-omat Blue XB-1).…”

Section: Western Immunoblottingmentioning

confidence: 99%

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Yang

Jia

et al. 2009

Laboratory Investigation

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156

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Hydrogen sulfide (H 2 S) has been traditionally known for its toxic effects on living organisms. The role of H 2 S in the homeostatic regulation of pancreatic insulin metabolism has been unclear. The present study is aimed at elucidating the effect of endogenously produced H 2 S on pancreatic insulin release and its role in diabetes development. Diabetes development in Zucker diabetic fatty (ZDF) rats was evaluated in comparison with Zucker fatty (ZF) and Zucker lean (ZL) rats. Pancreatic H 2 S production and insulin release were also assayed. It was found that H 2 S was generated in rat pancreas islets, catalyzed predominantly by cystathionine g-lyase (CSE). Pancreatic CSE expression and H 2 S production were greater in ZDF rats than in ZF or ZL rats. ZDF rats exhibited reduced serum insulin level, hyperglycemia, and insulin resistance. Inhibition of pancreatic H 2 S production in ZDF rats by intraperitoneal injection of DL-propargylglycine (PPG) for 4 weeks increased serum insulin level, lowered hyperglycemia, and reduced hemoglobin A1c level (Po0.05). Although in ZF rats it also reduced pancreatic H 2 S production and serum H 2 S level, PPG treatment did not alter serum insulin and glucose level. Finally, H 2 S significantly increased K ATP channel activity in freshly isolated rat pancreatic b-cells. It appears that insulin release is impaired in ZDF because of abnormally high pancreatic production of H 2 S. New therapeutic approach for diabetes management can be devised based on our observation by inhibiting endogenous H 2 S production from pancreas. KEYWORDS: diabetes; hydrogen sulfide; insulin release; K ATP channel; pancreas; type 2 diabetes mellitus Known as a swamp gas or 'rotten egg' gas, hydrogen sulfide (H 2 S) has yielded a public image of air pollutant for centuries. Physiological importance of H 2 S as a gasotransmitter has been realized for less than a decade. Endogenous production of H 2 S from L-cysteine is catalyzed by cystathionine b-synthase (CBS) and/or cystathionine g-lyase (CSE) with ammonium and pyruvate as co-products. 1 This process occurs in different organs and tissues, such as neuronal, vascular, and intestinal tissues. 2 Physiological concentrations of circulating H 2 S have been reported in the range of 45-300 mM. 1 At this physiological range, exogenous H 2 S has been shown to relax different vascular tissues, including isolated rat aortae and perfused mesenteric artery bed. 3-5 Altered cell proliferation or apoptosis induced by H 2 S has also been widely reported. [6][7][8][9][10] Endogenous production and physiological function of H 2 S in pancreas have been studied with identification of both CBS and CSE in rat pancreatic tissues or cloned rat pancreatic b-cell line. 11,12 In recent years, pathophysiological implications of the CSE/H 2 S system in diabetes have been reported. 12 CSE mRNA expression and H 2 S formation in rat pancreas was significantly increased after diabetes induction by streptozotocin injection. 12 CBS expression was reported in pancreatic acinar cells. 13 Y...

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“…The A10 vascular smooth muscle cell line, in which the Kir6.1/SUR2B channel was endogenously expressed (17,27), was loaded with BioGEE (250 M) for 1 h followed by an H 2 O 2 (750 M) challenge for 15 min. A strong Kir6.1-reactive band (ϳ32 kDa) was detected in the whole-cell lysate (Fig.…”

Section: H 2 O 2 Impaired Pinacidil-induced Vasodilation In Isolatedmentioning

confidence: 99%

Oxidative Stress Inhibits Vascular KATP Channels by S-Glutathionylation

Yang¹,

Shi

Cui

et al. 2010

Journal of Biological Chemistry

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The K ATP channel is an important player in vascular tone regulation. Its opening and closure lead to vasodilation and vasoconstriction, respectively. Such functions may be disrupted in oxidative stress seen in a variety of cardiovascular diseases, while the underlying mechanism remains unclear. Here, we demonstrated that S-glutathionylation was a modulation mechanism underlying oxidant-mediated vascular K ATP channel regulation. An exposure of isolated mesenteric rings to hydrogen peroxide (H 2 O 2 ) impaired the K ATP channel-mediated vascular dilation. In whole-cell recordings and inside-out patches, H 2 O 2 or diamide caused a strong inhibition of the vascular K ATP channel (Kir6.1/SUR2B) in the presence, but not in the absence, of glutathione (GSH). Similar channel inhibition was seen with oxidized glutathione (GSSG) and thiol-modulating reagents. The oxidant-mediated channel inhibition was reversed by the reducing agent dithiothreitol (DTT) and the specific deglutathionylation reagent glutaredoxin-1 (Grx1). Consistent with S-glutathionylation, streptavidin pull-down assays with biotinylated glutathione ethyl ester (BioGEE) showed incorporation of GSH to the Kir6.1 subunit in the presence of H 2 O 2 . These results suggest that S-glutathionylation is an important mechanism for the vascular K ATP channel modulation in oxidative stress.

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Selective expression of Kir6.1 protein in different vascular and non-vascular tissues

Cited by 31 publications

References 24 publications

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Oxidative Stress Inhibits Vascular KATP Channels by S-Glutathionylation

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Selective expression of Kir6.1 protein in different vascular and non-vascular tissues

Cited by 31 publications

References 24 publications

Consequences of cardiac myocyte-specific ablation of KATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of KATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Pancreatic islet overproduction of H2S and suppressed insulin release in Zucker diabetic rats

Oxidative Stress Inhibits Vascular KATP Channels by S-Glutathionylation

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Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits

Consequences of cardiac myocyte-specific ablation of K_ATPchannels in transgenic mice expressing dominant negative Kir6 subunits