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10.1152/ajprenal.00260.2014

http://scihub22266oqcxt.onion/10.1152/ajprenal.00260.2014
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suck abstract from ncbi


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pmid25080525
      Am+J+Physiol+Renal+Physiol 2014 ; 307 (7 ): F800-5
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  • Endogenous flow-induced superoxide stimulates Na/H exchange activity via PKC in thick ascending limbs #MMPMID25080525
  • Hong NJ ; Garvin JL
  • Am J Physiol Renal Physiol 2014[Oct]; 307 (7 ): F800-5 PMID25080525 show ga
  • Luminal flow stimulates Na reabsorption along the nephron and activates protein kinase C (PKC) which enhances endogenous superoxide (O(2) (-)) production by thick ascending limbs (TALs). Exogenously-added O(2) (-) augments TAL Na reabsorption, a process also dependent on PKC. Luminal Na/H exchange (NHE) mediates NaHCO?reabsorption. However, whether flow-stimulated, endogenously-produced O(2) (-) enhances luminal NHE activity and the signaling pathway involved are unclear. We hypothesized that flow-induced production of endogenous O2 (-) stimulates luminal NHE activity via PKC in TALs. Intracellular pH recovery was measured as an indicator of NHE activity in isolated, perfused rat TALs. Increasing luminal flow from 5 to 20 nl/min enhanced total NHE activity from 0.104 ± 0.031 to 0.167 ± 0.036 pH U/min, 81%. The O(2) (-) scavenger tempol decreased total NHE activity by 0.066 ± 0.011 pH U/min at 20 nl/min but had no significant effect at 5 nl/min. With the NHE inhibitor EIPA in the bath to block basolateral NHE, tempol reduced flow-enhanced luminal NHE activity by 0.029 ± 0.010 pH U/min, 30%. When experiments were repeated with staurosporine, a nonselective PKC inhibitor, tempol had no effect. Because PKC could mediate both induction of O2 (-) by flow and the effect of O(()-) on luminal NHE activity, we used hypoxanthine/xanthine oxidase to elevate O(2) (-). Hypoxanthine/xanthine oxidase increased luminal NHE activity by 0.099 ± 0.020 pH U/min, 137%. Staurosporine and the PKC?/?1-specific inhibitor Gö6976 blunted this effect. We conclude that flow-induced O(2) (-) stimulates luminal NHE activity in TALs via PKC?/?1. This accounts for part of flow-stimulated bicarbonate reabsorption by TALs.
  • |Animals [MESH]
  • |Cyclic N-Oxides [MESH]
  • |Hydrogen-Ion Concentration [MESH]
  • |Loop of Henle/*metabolism [MESH]
  • |Male [MESH]
  • |Protein Kinase C beta/*metabolism [MESH]
  • |Protein Kinase C-alpha/*metabolism [MESH]
  • |Rats [MESH]
  • |Rats, Sprague-Dawley [MESH]
  • |Sodium-Hydrogen Exchangers/*metabolism [MESH]
  • |Spin Labels [MESH]


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