American journal of physiology. Renal physiology
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Am. J. Physiol. Renal Physiol. · Aug 2004
Evidence for a role of protein kinase C-alpha in urine concentration.
In mouse kidney, the conventional protein kinase C (PKC) isoenzyme alpha is expressed in glomeruli, the cortical collecting duct (intercalated cells only), and medullary collecting duct. To get insights on its function, PKC-alpha knockout (-/-) and wild-type (+/+) mice were studied. When provided free access to water, PKC-alpha -/- mice showed approximately 50% greater urine flow rate and lower urinary osmolality in 24-h metabolic cage experiments despite a greater urinary vasopressin-to-creatinine ratio vs. ⋯ In comparison, the lower urinary osmolality observed in PKC-alpha -/- mice vs. wild-type mice under basal conditions persisted during water restriction for 36 h. In conclusion, PKC-alpha appears not to play a major role in renal sodium reabsorption but, consistent with its expression in the medullary collecting duct, contributes to urinary concentration in mice. Considering that PKC-beta I and -beta II are coexpressed with PKC-alpha in mouse medullary collecting duct, the present results indicate that conventional PKC isoenzymes cannot fully compensate for each other.
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Am. J. Physiol. Renal Physiol. · May 2004
Increased expression and apical targeting of renal ENaC subunits in puromycin aminonucleoside-induced nephrotic syndrome in rats.
Nephrotic syndrome is often accompanied by sodium retention and generalized edema. However, the molecular basis for the decreased renal sodium excretion remains undefined. We hypothesized that epithelial Na channel (ENaC) subunit dysregulation may be responsible for the increased sodium retention. ⋯ Moreover, the abundance of the alpha(1)-subunit of the Na-K-ATPase was decreased in the cortex and ISOM, but it remained unchanged in the IM. In conclusion, the increased or sustained expression of ENaC subunits combined with increased apical targeting in the DCT2, connecting tubule, and collecting duct are likely to play a role in the sodium retention associated with PAN-induced nephrotic syndrome. The decreased abundance of NHE3, BSC-1, TSC, and Na-K-ATPase may play a compensatory role to promote sodium excretion.
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Am. J. Physiol. Renal Physiol. · Apr 2004
Vascular localization of soluble epoxide hydrolase in the human kidney.
Epoxyeicosatrienoic acids are cytochrome P-450 metabolites of arachidonic acid with multiple biological functions, including the regulation of vascular tone, renal tubular transport, cellular proliferation, and inflammation. Epoxyeicosatrienoic acids are converted by soluble epoxide hydrolase into the corresponding dihydroxyeicosatrienoic acids, and epoxyeicosatrienoic acid hydration is regarded as one mechanism whereby their biological effects are eliminated. Previous animal studies indicate that soluble epoxide hydrolase plays an important role in the regulation of renal eicosanoid levels and systemic blood pressure. ⋯ Western blot analysis and functional assays confirmed the expression of soluble epoxide hydrolase in the human kidney. There were no obvious differences in soluble epoxide hydrolase expression between normal and diseased human kidney tissue in the samples examined. Our results indicate that soluble epoxide hydrolase is present in the human kidney, being preferentially expressed in the renal vasculature, and support an essential role for this enzyme in renal hemodynamic regulation and its potential utility as a target for therapeutic intervention.
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Am. J. Physiol. Renal Physiol. · Apr 2004
p38 MAP kinase mediates mechanically induced COX-2 and PG EP4 receptor expression in podocytes: implications for the actin cytoskeleton.
A dynamic cytoskeleton allows podocytes to withstand significant mechanical stress on elevation of intraglomerular capillary pressure (Pgc). However, vasoactive hormones, such as prostaglandin E2 (PGE2), may challenge the integrity of the actin cytoskeleton, alter podocyte morphology, and compromise glomerular permeability. PGE2 synthesis correlates with the onset of proteinuria and increased Pgc following reduced nephron mass. ⋯ Addition of PGE2 resulted in actin filament depolymerization observable only in stretched cells. Our results indicate that key components of the eicosanoid pathway are upregulated by mechanically stimulated p38 MAP kinase in podocytes. Enhanced EP4 receptor signaling may undermine podocyte cytoskeletal dynamics and thereby compromise filtration barrier function under conditions of increased Pgc.
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Am. J. Physiol. Renal Physiol. · Feb 2004
A1 adenosine receptor knockout mice exhibit increased renal injury following ischemia and reperfusion.
Controversy exists regarding the effect of A1 adenosine receptor (AR) activation in the kidney during ischemia and reperfusion (I/R) injury. We sought to further characterize the role of A1 ARs in modulating renal function after I/R renal injury using both pharmacological and gene deletion approaches in mice. A1 AR knockout mice (A1KO) or their wild-type littermate controls (A1WT) were subjected to 30 min of renal ischemia. ⋯ A1WT mice pretreated with the A1 AR antagonist or agonist demonstrated significantly worsened or improved renal function, respectively, after I/R injury. In addition, A1WT mice pretreated with DPCPX or CCPA showed significantly increased or reduced markers of renal inflammation, respectively (renal myeloperoxidase activity, renal tubular neutrophil infiltration, ICAM-1, TNF-alpha, and IL-1beta mRNA expression), while demonstrating no differences in indicators of apoptosis. In conclusion, we demonstrate that endogenous or exogenous preischemic activation of A1 ARs protects against renal I/R injury in vivo via mechanisms leading to decreased necrosis and inflammation.