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S Salehmoghaddam

Publications and source records attributed to S Salehmoghaddam.

8 recordsLinked to original sources
PubMed1985

Stimulation of Na+/H+ antiport is an early event in hypertrophy of renal proximal tubular cells.

Renal hypertrophy in vivo is achieved by an increase in protein content per cell and an increase in cell size with minimal hyperplasia. Hypertrophied renal tubular cells remain quiescent and demonstrate an increase in transcellular transport rates. This situation was simulated in vitro by exposing a confluent, quiescent primary culture of rabbit renal proximal tubular cells to either insulin, prostaglandin E1, or hypertonic NaCl for 24 or 48 hr. Protein per cell increased by 20-30% with little or no increase in [3H]thymidine incorporation into DNA. Mean cell volume was also increased in insulin- and hypertonic NaCl-treated but not in prostaglandin E1-treated cells. The lag period required to initiate DNA synthesis by a combination of insulin and hydrocortisone was the same in control and hypertrophied cells, indicating a quiescent state of the latter. Two hours of exposure to the growth stimuli increased amiloride-sensitive Na+ uptake, Na-dependent H+ efflux, and ouabain-sensitive Rb+ uptake, indicating that stimulation of Na+/H+ antiport (exchange) occurs as an early event in their action. Hypertrophied cells continued to demonstrate enhanced Na+/H+ antiport after the growth stimuli were removed for 3 hr, by which time their acute effects are reversed.

Alprostadil↗
PubMed1985

Mediation of the antiproliferative effect of cyclosporine on human lymphocytes by blockade of interleukin 2 biosynthesis.

Normal human peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin-P (PHAP) and cyclosporine (CsA) to investigate the mode of action of CsA on cellular proliferation. CsA at 1 microgram/ml exerted a marked inhibitory effect on PBMC responsiveness to PHAP. An antiproliferative effect of CsA was observed at the inductive phase of the cell cycle, but the drug was ineffective when it was added to cultures 24 hr after stimulation. In parallel with this inhibitory effect interleukin 2 (IL-2) production was inhibited. In contrast, IL-2 receptor was expressed on the CsA-treated cells, and the antiproliferative influence of the drug was completely reversed by addition of highly purified human IL-2 to the CsA-treated cells. Exogenous IL-2, however, did not restore cellular capacity to produce IL-2. This study suggests that CsA acts by inhibiting IL-2 production (via blockade of IL-2 gene expression) rather than by preventing the expression of the IL-2 receptor.

Cyclosporins↗
PubMed1985

Hypertrophy of basolateral Na-K pump activity in the proximal tubule of the remnant kidney.

Reduction of renal mass leads to an increase in the filtration rates of the remaining glomeruli and an increased rate of sodium and water reabsorption by the proximal tubules. To define the basis for this increased tubular reabsorptive capacity, the authors studied the relationship of basolateral sodium pump activity to the process of hypertrophy in the proximal tubule. They wished to determine whether the growth of the cell is associated with an increase in the number of basolateral Na-K pumps and whether basolateral membrane hypertrophy is symmetrical with respect to overall cell growth. Normal and subtotally nephrectomized rabbits (remnant kidneys) were studied. Ouabain-sensitive potassium uptake was measured in a highly purified suspension of cortical proximal tubules using 86Rb as a tracer. In normal kidneys Km was 0.99 +/- 0.30 mM and Vmax 83.1 +/- 13.7 nmoles X mg-1 X minute-1; in remnant kidneys Km was 0.63 +/- 0.10 mM and Vmax 49.2 +/- 10.9 nmoles X mg-1 X minute-1. These values are not significantly different from each other. In a suspension of isolated cortical proximal tubular cells, protein per cell was 172 +/- 23 pg in normal kidney and 450 +/- 56 pg in remnant kidneys, representing a 2.6-fold increase. The extrapolated Vmax for K uptake per cell was thus increased approximately 2.6-fold in the remnant kidney. This was confirmed by measuring the number of specific ouabain-binding sites in proximal tubular cells. This was also found to be approximately 2.5 to 3 times greater in the remnant kidney cells, the increase being proportional to the increase in cell protein. Histomorphometric analysis of S2 proximal convoluted tubules, which comprise the bulk of the cortical tissue, revealed that basolateral membrane area per cross-sectional area of tubule was increased in the remnant kidney. The mean absolute surface area per cross-section of tubule and the surface density (surface/volume ratio) of the basolateral membrane increased by 110 and 26%, respectively, whereas these changes in the luminal membrane were only 38 and -9%, respectively. Thus, the membrane areas of the proximal tubular cell hypertrophy asymmetrically. Although mitochondrial density does not increase in remnant tubules, mitochondrial volume increases significantly, possibly providing a source for the increased ATP required by the hypertrophied basolateral Na-K pump activity. In summary, the cells of the proximal convoluted tubule of the remnant kidney undergo functional and structural hypertrophy.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗