Induction of apoptosis in cultured hepatocytes and in the regressing liver by transforming growth factor-β1 occurs without activation of an endonuclease

Levels of transforming growth factor β and transforming growth factor β receptors in rat liver during growth, regression by apoptosis and neoplasia

“…33 Also carcinoma of various organs produce and release TGF-β protein to the serum in an endocrine fashion resulting in high plasma concentrations. 34,35 In our previous studies, the administration of a high iv dose of this cytokine caused apoptosis at a rate similar to that observed in involuting liver 22 ; the applied doses were calculated to lead to pronounced increases in hepatic levels of the TGF-β 1 protein.…”

“…[15][16][17][18][19] TGF-β 1 has been found to inhibit DNA synthesis in unaltered rat hepatocytes in vivo and in vitro, being active in the G 1 -phase of the cell cycle. [20][21][22][23] A further important function of TGF-β 1 is the induction of apoptosis in various cell lines in primary cultures of rat hepatocytes as well as in unaltered and preneoplastic hepatocytes in vivo. 22,24 After partial hepatectomy, TGF-β 1 mRNA was clearly elevated in the liver and presumably provided a signal to cease regeneration.…”

“…[20][21][22][23] A further important function of TGF-β 1 is the induction of apoptosis in various cell lines in primary cultures of rat hepatocytes as well as in unaltered and preneoplastic hepatocytes in vivo. 22,24 After partial hepatectomy, TGF-β 1 mRNA was clearly elevated in the liver and presumably provided a signal to cease regeneration. 20 In contrast, pronounced increases of TGF-β 1 mRNA were not seen during hyperplastic growth induced by phenobarbital, lead nitrate, or by peroxisome proliferators, and, therefore, did not seem to be involved in growth confinement in these models.…”

Fas-mediated apoptosis in mouse hepatocytes involves the processing and activation of caspases

“…[26][27][28] Little is known about how apoptosis is controlled in many of the latter organs. Hepatocytes or hepatoma cells may be induced to apoptose by cholestatic bile acids, 29 topoisomerase I inhibitors, 30 transforming growth factor ␤, 31 and tumor necrosis factor ␣. 32 Hepatocytes also express high levels of Fas antigen, which has been shown in vivo by intraperitoneal injection of anti-Fas antibody in mice to result in the death of the animals through massive liver damage.…”

Biochemical events in naturally occurring forms of cell death

“…Similarly. condensation of the chromatin at the membrane of apoptotic nuclei, an early morphological sign of apoptosis, have not been found associated with activation of an endonuclease [9,10], and several types of cells undergo apoptosis without DNA fragmentation [ll]. It has recently been demonstrated that the Ca"/Mg''-dependent endonuclease is functionally and antigenically identical to DNase I [12].…”