<i>S</i>‐Glutathionylation underscores the modulation of the heteromeric Kir4.1–Kir5.1 channel in oxidative stress

Jin, Xin; Yu, Lei; Wu, Yang; Zhang, Shuang; Shi, Zhenda; Chen, Xianfeng; Yang, Yang; Zhang, Xiaoli; Jiang, Chun

doi:10.1113/jphysiol.2012.236885

Cited by 14 publications

(13 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Patch clamp experiments were performed as described previously at room temperature [23] [24] [25]. In brief, 1 2 mm borosilicate glass capillaries were fire-polished to make patch pipettes of 2-5 MΩ resistance.…”

Section: Methodsmentioning

confidence: 99%

Acute exposure of methylglyoxal leads to activation of KATP channels expressed in HEK293 cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

Diabetes is characterized by hyperglycemia and excessive production of metabolites. One of these metabolites is the highly reactive carbonyl, methylglyoxal (MGO). MGO can readily react with biomolecules leading to cellular dysfunction. Here we showed that acute MGO application led to a dose-dependent activation of KATP channels, a major vascular tone regulator and a critical pharmacological target for treating diabetes. Both Kir6.1 and Kir6.2 containing KATP channels were targeted by MGO in a SUR subunit independent manner. Single channel analysis showed that MGO mediated KATP channel activation via enhancement of channel open probability, leaving the channel conductance unaltered. This modulation appeared to be due to the direct interaction of MGO with the KATP channel, without the need for additional cell signaling pathways. Moreover, MGO mediated KATP channel activity was completely reversed with bath solution washout. Taken together, these data suggest that acute exposure to MGO activates KATP channels through direct, non-covalent and reversible interactions with the Kir6.x subunit, suggest a potential target for pharmacological intervention towards vascular complications of diabetes.

show abstract

Section: Methodsmentioning

confidence: 99%

Acute exposure of methylglyoxal leads to activation of KATP channels expressed in HEK293 cells

et al. 2013

Self Cite

View full text Add to dashboard Cite

show abstract

“…Jin et al has found that the presence of Kir5.1 in the Kir4-Kir5 heterodimeric channel enables channel sensitivity to Sglutathionylation. Using diamide or H 2 O 2 together with GSH, it was found that the Kir4-Kir5 channel could be inhibited via S-glutathionylation while the homodimeric Kir4.1 channel is not sensitive to this modification (55). Further study showed that Cys158 in the S6 helix of Kir5.1 is the major residue for S-glutathionylation (Fig.…”

Section: S-glutathionylation Of Kir4-kir5 Channelmentioning

confidence: 99%

“…4A, B). In addition, it was demonstrated that one GSH moiety is sufficient to block the channel activity and S-glutathionylation occurs when the channel is in its open state (55).…”

Section: S-glutathionylation Of Kir4-kir5 Channelmentioning

confidence: 99%

See 1 more Smart Citation

S-Glutathionylation of Ion Channels: Insights into the Regulation of Channel Functions, Thiol Modification Crosstalk, and Mechanosensing

Yang

Jin²,

Jiang³

2014

Antioxidants & Redox Signaling

Self Cite

View full text Add to dashboard Cite

Significance: Ion channels control membrane potential, cellular excitability, and Ca ++ signaling, all of which play essential roles in cellular functions. The regulation of ion channels enables cells to respond to changing environments, and post-translational modification (PTM) is one major regulation mechanism. Recent Advances: Many PTMs (e.g., S-glutathionylation, S-nitrosylation, S-palmitoylation, S-sulfhydration, etc.) targeting the thiol group of cysteine residues have emerged to be essential for ion channels regulation under physiological and pathological conditions. Critical Issues: Under oxidative stress, S-glutathionylation could be a critical PTM that regulates many molecules. In this review, we discuss S-glutathionylation-mediated structural and functional changes of ion channels. Criteria for testing S-glutathionylation, methods and reagents used in ion channel S-glutathionylation studies, and thiol modification crosstalk, are also covered. Mechanotransduction, and S-glutathionylation of the mechanosensitive K ATP channel, are discussed. Future Directions: Further investigation of the ion channel S-glutathionylation, especially the physiological significance of S-glutathionylation and thiol modification crosstalk, could lead to a better understanding of the thiol modifications in general and the ramifications of such modifications on cellular functions and related diseases. Antioxid. Redox Signal. 20, 937-951.

show abstract

“…by acting in concert with aquaporin-4 (AQP4) to maintain osmotic homoeostasis [2] . Furthermore, KIR4.1 channels colocalize with AQP4, the water channel expressed on the end feet of astrocytes [3,4] .…”

mentioning

confidence: 99%

Anti-KIR4.1 Antibodies in Chinese Patients with Central Nervous System Inflammatory Demyelinating Disorders

Zhong

Liang²,

Tao³

et al. 2016

Neuroimmunomodulation

View full text Add to dashboard Cite

Objectives: The aim of this study was to explore the frequency of KIR4.1 antibodies in patients with multiple sclerosis (MS) and in control groups using a cell-based assay. Materials and Methods: A transfected HEK-293A cell line expressing KIR4.1 was established to test for the presence of KIR4.1 antibodies in blood serum. We tested 904 subjects, including 188 patients with MS, 264 patients with neuromyelitis optica spectrum disorders (NMOSD), 209 patients with other inflammatory neurologic disease (OIND), 203 patients with other noninflammatory neurological disease (OND), and 40 healthy controls. Results: KIR4.1 antibodies were present in 23 of the 188 (12.2%) MS patients, 42 of the 264 (15.9%) NMOSD patients, 32 of the 209 (15.3%) OIND patients, 24 of the 203 (11.8%) OND patients, and 2 of the 40 (5%) healthy controls. There were no significant differences among the MS and control groups (p = 0.279). Conclusions: Anti-KIR4.1 antibody, as determined by a cell-based assay, is not a specific biomarker for MS.

show abstract

S‐Glutathionylation underscores the modulation of the heteromeric Kir4.1–Kir5.1 channel in oxidative stress

Cited by 14 publications

References 39 publications

Acute exposure of methylglyoxal leads to activation of KATP channels expressed in HEK293 cells

Acute exposure of methylglyoxal leads to activation of KATP channels expressed in HEK293 cells

S-Glutathionylation of Ion Channels: Insights into the Regulation of Channel Functions, Thiol Modification Crosstalk, and Mechanosensing

Anti-KIR4.1 Antibodies in Chinese Patients with Central Nervous System Inflammatory Demyelinating Disorders

Contact Info

Product

Resources

About