Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0920646 (renal ischemia)
 2,515 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diverse physical and chemical stimuli can activate sphingomyelinases (SMases), resulting in sphingomyelin (SM) hydrolysis with ceramide release. Since ceramide can profoundly impact a host of homeostatic mechanisms, the concept of a "SM (or SMase) signaling pathway" has emerged. We recently documented that ceramide levels fall abruptly during renal ischemia, and then rebound to twice normal values during early reperfusion (30 to 90 min) Therefore, the present study assessed whether these ceramide changes are paralleled, and hence potentially mediated, by comparable changes in SMase activity. Mice were subjected to 45 minutes of renal ischemia +/- 30 minutes, 90 minutes, or 24 hours of reperfusion. Renal cortices (or isolated proximal tubules) were then assayed for SMase activity (acidic, neutral forms). To characterize whether early post-ischemic ceramide increments are a relatively persistent event, ceramide was assayed following a 24-hour reperfusion period. Finally, to assess whether the observed perturbations were unique to post-ischemic injury, SMase and ceramide were quantified in the setting of glycerol-induced myohemoglobinuria and anti-glomerular basement membrane (alpha GBM) antibody-induced acute renal failure (ARF). Ischemia induced abrupt declines (approximately 50%) in both acidic and neutral SMase activities, and these persisted in an unremitting fashion throughout 24 hours of reperfusion. Nevertheless, increased ceramide expression (2x normal) resulted. Myohemoglobinuria also suppressed acidic/neutral SMases, and again, "paradoxical" ceramide increments were observed. Finally, alpha GBM nephritis increased ceramide levels, but in this instance, a correlate was increased SMase activity. These results suggest that: (1) ceramide is an acute renal "stress rectant" increasing in response to diverse renal insults; (2) this response may occur independently of the classic SM pathway, since the ceramide increments can seemingly be dissociated from increased SMase activity; and (3) given the well documented impact of ceramide and the SM(ase) pathway on apoptosis, cell proliferation, differentiation, and tissue inflammation, the present results have potentially broad ranging implications for the induction and evolution of diverse forms of ARF.
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PMID:Altered sphingomyelinase and ceramide expression in the setting of ischemic and nephrotoxic acute renal failure. 950 28

The elastic properties of renal glomeruli and their capillaries permit them to maintain structural integrity in the presence of variable hemodynamic forces. Measured by micro-indentation, glomeruli have an elastic modulus (E, Young's modulus) of 2.1 kPa, and estimates from glomerular perfusion studies suggest that the E of glomeruli is between 2 and 4 kPa. F-actin depolymerization by latrunculin, inhibition of acto-myosin contractility by blebbistatin, reduction in ATP synthesis, and reduction of the affinity of adhesion proteins by EDTA reduced the glomerular E to 1.26, 1.7, 1.5, and 1.43 kPa, respectively. Actin filament stabilization with jasplakinolide and increasing integrin affinity with Mg2+ increased E to 2.65 and 2.87 kPa, respectively. Alterations in glomerular E are reflected in commensurate changes in F/G actin ratios. Disruption of vimentin intermediate filaments by withaferin A reduced E to 0.92 kPa. The E of decellularized glomeruli was 0.74 kPa, indicating that cellular components of glomeruli have dominant effects on their elasticity. The E of glomerular basement membranes measured by magnetic bead displacement was 2.4 kPa. Podocytes and mesangial cells grown on substrates with E values between 3 and 5 kPa had actin fibers and focal adhesions resembling those of podocytes in vivo. Renal ischemia and ischemia-reperfusion reduced the E of glomeruli to 1.58 kPa. These results show that the E of glomeruli is between 2 and 4 kPa. E of the GBM, 2.4 kPa, is consistent with this value, and is supported by the behavior of podocytes and mesangial cells grown on variable stiffness matrices. The podocyte cytoskeleton contributes the major component to the overall E of glomeruli, and a normal E requires ATP synthesis. The reduction in glomerular E following ischemia and in other diseases indicates that reduced glomerular E is a common feature of many forms of glomerular injury and indicative of an abnormal podocyte cytoskeleton.
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PMID:Biochemical and Cellular Determinants of Renal Glomerular Elasticity. 2794 3