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To determine the predominant pathway for transepithelial osmotic water flow, the transepithelial osmotic water permeability [Pf(TE)] and the apparent dimensions of paracellular pores and slits were determined in rat proximal convoluted tubules microperfused in vivo. To measure Pf(TE), tubules were perfused with a hyposmotic, cyanide-containing solution.(More)
Increased Na/H antiporter activity has been demonstrated after in vivo chronic metabolic acidosis as well as in vitro acid preincubation of cultured rabbit renal tubule cells. To study the underlying molecular mechanisms of this adaptive increase in Na/H antiporter activity, the present studies examined the effect of low pH media on Na/H antiporter activity(More)
When renal epithelial cells are exposed to epidermal growth factor-transforming growth factor-beta1 (EGF-TGF-beta1) the typical EGF-mediated hyperplastic growth response is converted to a hypertrophic growth response. Hypertrophy in this setting involves cell entrance into G(1), but arrest of cell cycle progression at the G(1)/S interface. Late G(1) arrest(More)
In the absence of exogenous glucocorticoids, decreasing media pH (from 7.4 to 6.8) for 24 hours increased the Na+/H+ exchanger 3 (NHE3) activity in opossum kidney (OKP) cells. 10(-7) M and 10(-8) M hydrocortisone increased NHE3 activity, and in their presence, acid incubation further increased NHE3 activity. Hydrocortisone (10(-9) M) had no effect on NHE3(More)
BACKGROUND In the renal proximal tubule, chronic acidosis causes increases in apical membrane NHE3 activity, which serve to increase transepithelial H+ secretion and return systemic pH to normal levels. Incubation of cultured renal epithelial cells in acid media activates c-Src. METHODS OKP cells were incubated in control (pH 7.4) or acid (7.0) media, and(More)
BACKGROUND Two mechanisms exist for inducing renal proximal tubule hypertrophy. One is characterized by regulation of the G1 cell cycle kinase (cell cycle-dependent mechanism), while the other mechanism involves an imbalance between rates of protein synthesis and degradation, and occurs independently of cell cycle kinase regulation (cell cycle-independent(More)
BACKGROUND High protein diets are believed to cause kidney stone formation and bone loss, but the mechanisms mediating these changes are unknown. The purpose of this study was to create an animal model of animal protein excess and to evaluate the response of kidney and bone to the dietary protein load. METHODS Rats (12 per group) were pair-fed with a high(More)
Chronic metabolic acidosis increases proximal tubular citrate uptake and metabolism. The present study addressed the effect of chronic metabolic acidosis on a cytosolic enzyme of citrate metabolism, ATP citrate lyase. Chronic metabolic acidosis caused hypocitraturia in rats and increased renal cortical ATP citrate lyase activity by 67% after 7 d. Renal(More)
BACKGROUND Diabetes mellitus-induced nephromegaly is thought to involve both hyperplastic and hypertrophic proximal tubule cell growth. The temporal relationship between these growth patterns and the mechanisms that mediate them are unknown. METHODS Renal growth was assayed in isolated renal proximal tubules harvested from diabetic rats. Diabetes mellitus(More)