Y S Zhang1, Z G Tu. 1. Department of Clinical Biochemistry, Chongqing University of Medical Sciences, Chongqing 400016, China.
Abstract
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.
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.