Transforming growth factor β1 increases the number of apoptotic bodies and decreases intracellular pH in isolated periportal and perivenular rat hepatocytes

Transforming growth factor beta 1 (TGF β1 ) is involved in promoting cell death by apoptosis in the liver, whereas the activation of Na + /H + exchanger has been related to cell proliferation. The aim of this study was to gain information on the effects of TGF β1 on intracellular pH and Na + H + exchange activity in isolated periportal (PP) and perivenular (PV) rat hepatocytes using the pH‐sensitive dye BCECF in a perfused subconfluent hepatocyte monolayer. Steady‐state intracellular pH (pH i ) in a bicarbonate‐free solution (HEPES) were 7.17 ± 0.031 in PP and 7.15 ± 0.041 in PV cells. Treatment with TGF β1 (120 pmol/L) for 7 hours increased the number of apoptotic bodies by 25% and 38%, and decreased steady‐state pH i to 7.11 ± 0.018 ( P = .05) and to 7.07 ± 0.021 ( P ± .02), respectively, in PP and PV hepatocytes. In HEPES, cells recovered from an acid load, extruding protons at a rate (J H ) of 4.85 ± 1.01 mmol/L/min in PP cells and of 4.91 ± 0.99 mmol/L/min in PV hepatocytes. This recovery appeared amiloride inhibitable (1 mmol/L). Culture with TGF β1 for 7 hours induced (in HEPES) a decrease of pH i recovery rate from an acid load more in PV (by 46%) than in PP hepatocytes (by 35%, P ± .05). Acute administration of epidermal growth factor (EGF) (10 to 100 ng/mL) induced an increase in Na + /H + exchange activity by 32% and 27%, respectively, in PP and PV cells compared with controls. In contrast, in cells cultured for 7 hours with 120 pmol/L TGF β1 , the acute administration of EGF slightly increased Na + /H + exchange activity (by 18%, P ± .05) only in PP cells. This study demonstrates that pH i and Na + /H + exchange activity are decreased by TGF β1 , which increases the number of apoptotic bodies in periportal and perivenular rat hepatocyte primary cultures. (Hepatology 1995; 22:1488–1498).