Mitogen-Activated Protein Kinases Inhibit the ROMK (Kir 1.1)-Like Small Conductance K Channels in the Cortical Collecting Duct

Babilonia, Elisa; Li, Dimin; Wang, Zhijian; Sun, Peng; Lin, Dao‐Hong; Jin, Yan; Wang, Wenhui

doi:10.1681/asn.2006050426

Cited by 42 publications

(51 citation statements)

References 41 publications

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“…We and others have shown that the K restriction decreased ROMK channel activity and caused the internalization of ROMK channels. 13,26,27 Although the molecular mechanism by which low K suppresses ROMK channel activity and renal K secretion is not completely understood, our previous study suggests that superoxide anions and related products are signaling molecules that mediate the effect of low K intake on ROMK channels and renal K secretion 4,7,28 Furthermore, we show that P38 and ERK MAPK and PTK are involved in mediating the effect of superoxide anions on ROMK channels. 4,7,28 The role of P38 and ERK MAPK in mediating the effect of low K intake and superoxide anions on ROMK channels is supported by several lines of evidence: (1) Application of hydrogen peroxide stimulated the phosphorylation of ERK and P38 MAPK in M-1 cells; (2) inhibition of superoxide anion production with tempol abolished the stimulatory effect of low K intake on the phosphorylation of P38 and ERK; and (3) suppression of P38 and ERK MAPK increased ROMK channel activity and diminished the inhibition of ROMK channels induced by hydrogen peroxide in the CCD.…”

Section: Discussionmentioning

confidence: 65%

“…13,26,27 Although the molecular mechanism by which low K suppresses ROMK channel activity and renal K secretion is not completely understood, our previous study suggests that superoxide anions and related products are signaling molecules that mediate the effect of low K intake on ROMK channels and renal K secretion 4,7,28 Furthermore, we show that P38 and ERK MAPK and PTK are involved in mediating the effect of superoxide anions on ROMK channels. 4,7,28 The role of P38 and ERK MAPK in mediating the effect of low K intake and superoxide anions on ROMK channels is supported by several lines of evidence: (1) Application of hydrogen peroxide stimulated the phosphorylation of ERK and P38 MAPK in M-1 cells; (2) inhibition of superoxide anion production with tempol abolished the stimulatory effect of low K intake on the phosphorylation of P38 and ERK; and (3) suppression of P38 and ERK MAPK increased ROMK channel activity and diminished the inhibition of ROMK channels induced by hydrogen peroxide in the CCD. 28 The evidence to support the role of PTK in mediating the effect of low K intake and superoxide anions on ROMK channel activity 26 includes the following: (1) Low K intake significantly increased the expression of Src family PTK and suppression of superoxide anions abolished the effect of low K intake on PTK expression, 4 (2) increased PTK activity enhanced the tyrosine phosphorylation of ROMK channels 29 and enhanced the internalization of ROMK channels, 8 and (3) inhibition of PTK attenuated the hydrogen peroxide-induced inhibition of ROMK channels in the CCD.…”

Section: Discussionmentioning

confidence: 65%

“…28 Because low K-induced increases in PTK expression occurs later than that of the phosphorylation of P38 and ERK MAPK, it is possible that the inhibitory effect of low K intake on ROMK channels and renal K secretion is first achieved by activation of MAPK. 7 However, it is safe to conclude that superoxide anions mediate the effect of low K intake on ROMK channels and renal K secretion through MAPK and PTK.…”

Section: Discussionmentioning

confidence: 99%

“…4 Superoxide or related products have been shown to activate mitogen-activated protein kinase (MAPK) such as P38 and extracellular signal-regulated kinase (ERK), 5 stimulate protein tyrosine kinase (PTK) activity, 6 and augment the expression of Src family PTK in the kidney. 7 We have also demonstrated that P38 and ERK MAPK and PTK inhibited ROMK channels in the cortical collecting duct (CCD). 7,8 The role of superoxide in mediating the effect of K-depletion on ROMK channels and renal K secretion is best indicated by experiments in which decreasing superoxide levels with tempol treatment increased ROMK channel activity and renal K loss.…”

mentioning

confidence: 94%

“…7 We have also demonstrated that P38 and ERK MAPK and PTK inhibited ROMK channels in the cortical collecting duct (CCD). 7,8 The role of superoxide in mediating the effect of K-depletion on ROMK channels and renal K secretion is best indicated by experiments in which decreasing superoxide levels with tempol treatment increased ROMK channel activity and renal K loss. 4 The superoxide anions are generated by the univalent reduction of triple-state molecular oxygen mediated by NADPH and xanthine oxidase.…”

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confidence: 94%

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Role of gp91phox-Containing NADPH Oxidase in Mediating the Effect of K Restriction on ROMK Channels and Renal K Excretion

Babilonia

Lin²,

Zhang³

et al. 2007

Journal of the American Society of Nephrology

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Previous study has demonstrated that superoxide and the related products are involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity in the cortical collecting duct (CCD). This study investigated the role of gp91 phox -containing NADPH oxidase (NOXII) in mediating the effect of low K intake on renal K excretion and ROMK channel activity in gp91(Ϫ/Ϫ) mice. K depletion increased superoxide levels, phosphorylation of c-Jun, expression of c-Src, and tyrosine phosphorylation of ROMK in renal cortex and outer medulla in wild-type (WT) mice. In contrast, tempol treatment in WT mice abolished whereas deletion of gp91 significantly attenuated the effect of low K intake on superoxide production, c-Jun phosphorylation, c-Src expression, and tyrosine phosphorylation of ROMK. Patch-clamp experiments demonstrated that low K intake decreased mean product of channel number (N) and open probability (P) (NP o ) of ROMK channels from 1.1 to 0.4 in the CCD. However, the effect of low K intake on ROMK channel activity was significantly attenuated in the CCD from gp91(Ϫ/Ϫ) mice and completely abolished by tempol treatment. Immunocytochemical staining also was used to examine the ROMK distribution in WT, gp91(Ϫ/Ϫ), and WT mice with tempol treatment in response to K restriction. K restriction decreased apical staining of ROMK in WT mice. In contrast, a sharp apical ROMK staining was observed in the tempol-treated WT or gp91(Ϫ/Ϫ) mice. Metabolic cage study further showed that urinary K loss is significantly higher in gp91(Ϫ/Ϫ) mice than in WT mice. It is concluded that superoxide anions play a key role in suppressing K secretion during K restriction and that NOXII is involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity.

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Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 65%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 94%

mentioning

confidence: 94%

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Role of gp91phox-Containing NADPH Oxidase in Mediating the Effect of K Restriction on ROMK Channels and Renal K Excretion

Babilonia

Lin²,

Zhang³

et al. 2007

Journal of the American Society of Nephrology

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In VivoandEx VivoAnalysis of Tubule Function

Stockand

Vallon²,

Ortíz

2012

Comprehensive Physiology

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Analysis of tubule function with in vivo and ex vivo approaches has been instrumental in revealing renal physiology. This work allows assignment of functional significance to known gene products expressed along the nephron, primary of which are proteins involved in electrolyte transport and regulation of these transporters. Not only we have learned much about the key roles played by these transport proteins and their proper regulation in normal physiology but also the combination of contemporary molecular biology and molecular genetics with in vivo and ex vivo analysis opened a new era of discovery informative about the root causes of many renal diseases. The power of in vivo and ex vivo analysis of tubule function is that it preserves the native setting and control of the tubule and proteins within tubule cells enabling them to be investigated in a "real-life" environment with a high degree of precision. In vivo and ex vivo analysis of tubule function continues to provide a powerful experimental outlet for testing, evaluating, and understanding physiology in the context of the novel information provided by sequencing of the human genome and contemporary genetic screening. These tools will continue to be a mainstay in renal laboratories as this discovery process continues and as we continue to identify new gene products functionally compromised in renal disease.

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Regulation of Transport in the Connecting Tubule and Cortical Collecting Duct

Staruschenko

2012

Comprehensive Physiology

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The central goal of this overview article is to summarize recent findings in renal epithelial transport, focusing chiefly on the connecting tubule (CNT) and the cortical collecting duct (CCD). Mammalian CCD and CNT are involved in fine tuning of electrolyte and fluid balance through reabsorption and secretion. Specific transporters and channels mediate vectorial movements of water and solutes in these segments. Although only a small percent of the glomerular filtrate reaches the CNT and CCD, these segments are critical for water and electrolyte homeostasis since several hormones, e.g. aldosterone and arginine vasopressin, exert their main effects in these nephron sites. Importantly, hormones regulate the function of the entire nephron and kidney by affecting channels and transporters in the CNT and CCD. Knowledge about the physiological and pathophysiological regulation of transport in the CNT and CCD and particular roles of specific channels/transporters has increased tremendously over the last two decades. Recent studies shed new light on several key questions concerning the regulation of renal transport. Precise distribution patterns of transport proteins in the CCD and CNT will be reviewed, and their physiological roles and mechanisms mediating ion transport in these segments will be also covered. Special emphasis will be given to pathophysiological conditions appearing as a result of abnormalities in renal transport in the CNT and CCD.

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Mitogen-Activated Protein Kinases Inhibit the ROMK (Kir 1.1)-Like Small Conductance K Channels in the Cortical Collecting Duct

Cited by 42 publications

References 41 publications

Role of gp91phox-Containing NADPH Oxidase in Mediating the Effect of K Restriction on ROMK Channels and Renal K Excretion

Role of gp91phox-Containing NADPH Oxidase in Mediating the Effect of K Restriction on ROMK Channels and Renal K Excretion

In VivoandEx VivoAnalysis of Tubule Function

Regulation of Transport in the Connecting Tubule and Cortical Collecting Duct

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