Jeong, DH Lee, SJ Lee, JH Bae, IH Jeong, KS Jang, JJ Lim, IK Kim, MR Lee, MJ Lee, YS 2024-01-21T13:04:47Z 2024-01-21T13:04:47Z 2021-09-01 2001-01 0815-9319 https://pubs.kist.re.kr/handle/201004/140833 Background and Aims: Protein kinase C (PKC) plays a key role in the alteration of signal transduction in the liver, which may contribute to the development of liver cirrhosis. The aim of the present study was to examine the subcellular redistribution of PKC isozymes in rat liver cirrhosis, which is induced by two different cirrhotic chemical agents, carbon tetrachloride (CCl4) and thioacetamide (TAA). Methods and Results: Thioacetamide and CCl4 were administered to rats for 8 and 30 weeks, respectively before rats were killed and autopsies performed at 9, 20 and 30 weeks later. The TAA induced a fibrotic pattern in the liver that differed from that produced by CCl4, notably in the formation of fibrous connective tissue and the proliferation of bile ductule cells. Cholangiofibrosis and clear-cell foci were also observed in TAA-treated rats at 30 weeks. Histological examination revealed that severe cirrhotic changes were present 9 weeks after the commencement of CCl4 treatment and 30 weeks after TTA treatment. Discussion: When the subcellular redistribution of PKC isozymes (PKC alpha, -beta1, -delta, and -epsilon) was examined, all the PKC isozymes in CCl4-treated rats were found to be translocated to the membrane fraction, which may mean PKC activation, and then downregulated by proteolytic degradation after 9 weeks of treatment, which coincided with peak cirrhotic changes. All rats treated with CCl4 recovered to the control level after 20 weeks of treatment, In the case of TAA-treated rats, PKC isozymes were translocated to the particulate fraction of the liver after 9 weeks of treatment and this persisted in most of the rats for the duration of the experiment. Conclusions: From these results, it would appear that PKC translocation preceded morphologic changes, and that an altered subcellular distribution of the PKC isozyme may be associated with the response to liver damage and carcinogenesis. (C) 2001 Blackwell Science Asia Pty Ltd. English BLACKWELL SCIENCE ASIA HEPATOCARCINOGENESIS DIFFERENTIATION EXPRESSION COLLAGEN ISOFORMS CANCER Subcellular redistribution of protein kinase C isozymes is associated with rat liver cirrhotic changes induced by carbon tetrachloride or thioacetamide Article 10.1046/j.1440-1746.2001.02364.x 1 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, v.16, no.1, pp.34 - 40 JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 16 1 34 40 scie scopus 000167674800006 Gastroenterology & Hepatology Gastroenterology & Hepatology Article HEPATOCARCINOGENESIS DIFFERENTIATION EXPRESSION COLLAGEN ISOFORMS CANCER CCl4 thioacetamide rat-liver cirrhosis protein kinase C isozymes subcellular distribution