Expression of Bcl-2 and Bax in hypokalemic nephropathy in rats

Potassium depletion results in hyperplasia of renal tubular and interstitial cells in humans and animals, and potassium repletion induces rapid regression of hyperplasia. Apoptosis participates importantly in this reduction of cell number, although we have observed tubular and interstitial apoptosis in rats during potassium depletion as well.

To investigate mechanisms of apoptosis in this model, we assessed expression of Bcl-2 and Bax, using immunohistochemistry and reverse transcriptase-polymerase chain reaction (RT-PCR).

Cell proliferation identifiable by labeling with 5-bromo 2'-deoxyuridine was prominent in tubular and interstitial cells of the cortex and outer medulla (OM) 7 days after potassium depletion. Simultaneously present apoptotic cells identified by light microscopy, electron microscopy, and nick end labeling were located mainly in the OM. Seven days after potassium repletion, apoptotic cells increased again but proliferating cells decreased. Bcl-2 protein distributed in the tubules of the OM was significantly decreased in potassium-depleted and potassium-repleted rats compared with control rats, while immunoreactivity for Bax protein tended to increase above control levels in potassium-depleted rats. RT-PCR for bcl-2 and bax demonstrated a significant decrease in levels of bcl-2 mRNA in potassium-depleted and potassium-repleted rats relative to those in controls. Expression of bax mRNA in potassium-depleted and potassium-repleted rats tended to increase, while ratios of bcl-2 mRNA to bax mRNA significantly decreased.

These results suggest that apoptosis is associated with progression and regression of cellular proliferation in hypokalemic nephropathy, and a decrease in Bcl-2 may be involved in promoting this apoptotic process.