Regulation of alpha 1-adrenoceptor on rat hepatocyte apoptosis induced by D-galactosamine and lipopolysaccharide.

AIM

To study the regulation of alpha 1-adrenoceptor on the biochemical changes involved in hepatocyte apoptosis induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS).

METHODS

Prazosin (Pra) 4 mg.kg-1 ig was administrated 1 h before i.p. D-GalN 600 mg.kg-1 and LPS 1 microgram.kg-1. The morphological changes of hepatocytes were observed. The concentrations of intracellular free ion calcium ([Ca2+]i), the expression of secretory phospholipase A2 (sPLA2) and cytosolic phospholipase A2 (cPLA2) in hepatocytes, and the levels of alanine aminotransferase (ALT), sPLA2, and tumor necrosis factor-alpha (TNF-alpha) in serum were all assayed.

RESULTS

The amounts of apoptotic bodies and apoptotic hepatocytes were reduced by the treatment of Pra (P < 0.01). The levels of [Ca2+]i, ALT, sPLA2, and TNF-alpha were (605 +/- 95) nmol.L-1, (214 +/- 141) u.L-1, (11.2 +/- 1.1)%, and (314 +/- 93) ng.L-1, respectively. Pra could decrease all the above biochemical changes to (364 +/- 61) nmol.L-1, (157 +/- 99) u.L-1, (7.9 +/- 1.6)%, and (156 +/- 62) ng.L-1 (all P < 0.05), respectively. The expression of cPLA2 was reduced by Pra treatment, too, but Pra had no significant effect on the expression of sPLA2.

CONCLUSION

The apoptosis in rat hepatocytes is regulated by alpha 1-AR signal transduction pathway including changes in [Ca2+]i, sPLA2 secretion, and cPLA2 expression. TNF-alpha is also involved in rat hepatocyte apoptotic regulation.