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Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells.
Hepatology. 1999 Nov; 30(5):1215-22.Hep

Abstract

Transforming growth factor-beta1 (TGF-beta1) has been shown to induce apoptosis in normal or transformed hepatocytes. To elucidate the biochemical pathways leading to apoptosis induced by TGF-beta1 in human hepatoma cells (HuH-7), we examined the expression of Bcl-2-related proteins and X-chromosome-linked inhibitor of apoptosis (XIAP), and activation of the caspase cascade following TGF-beta1 treatment. Bcl-xL expression began to decline at 12 hours after TGF-beta1 treatment and progressively decreased to very low levels in a time-dependent manner. Bax expression showed a little change throughout the experiment. On the other hand, activation of caspase-8 was clearly observed at 36 hours after TGF-beta1 treatment, followed by activation of caspase-9, and caspase-3 was activated at 48 hours after treatment at which time apoptosis of HuH-7 cells was observed. TGF-beta1 significantly decreased XIAP expression in HuH-7 cells. Addition of an inhibitor of caspase-8 or caspase-3 (IETD-FMK or DEVD-CHO) markedly inhibited TGF-beta1-induced apoptosis of HuH-7 cells. Fas/Fas ligand (FasL) interactions in HuH-7 cells were not involved in the apoptotic process. Furthermore, epidermal growth factor (EGF) also completely inhibited TGF-beta1-induced apoptosis of HuH-7 cells by inhibiting activation of the caspase cascade. Our results suggested that activation of caspase-3 initiated through caspase-8 activation is involved in the apoptotic process induced by TGF-beta1 in HuH-7 cells. Our results also showed that down-regulation of the expression of Bcl-xL and XIAP by TGF-beta1 may facilitate activation of caspase-3 in these cells.

Authors+Show Affiliations

Department of Clinical Pharmacology, Nagasaki University School of Medicine, Nagasaki, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

10534343

Citation

Shima, Y, et al. "Activation of Caspase-8 in Transforming Growth Factor-beta-induced Apoptosis of Human Hepatoma Cells." Hepatology (Baltimore, Md.), vol. 30, no. 5, 1999, pp. 1215-22.
Shima Y, Nakao K, Nakashima T, et al. Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells. Hepatology. 1999;30(5):1215-22.
Shima, Y., Nakao, K., Nakashima, T., Kawakami, A., Nakata, K., Hamasaki, K., Kato, Y., Eguchi, K., & Ishii, N. (1999). Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells. Hepatology (Baltimore, Md.), 30(5), 1215-22.
Shima Y, et al. Activation of Caspase-8 in Transforming Growth Factor-beta-induced Apoptosis of Human Hepatoma Cells. Hepatology. 1999;30(5):1215-22. PubMed PMID: 10534343.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Activation of caspase-8 in transforming growth factor-beta-induced apoptosis of human hepatoma cells. AU - Shima,Y, AU - Nakao,K, AU - Nakashima,T, AU - Kawakami,A, AU - Nakata,K, AU - Hamasaki,K, AU - Kato,Y, AU - Eguchi,K, AU - Ishii,N, PY - 1999/10/26/pubmed PY - 1999/10/26/medline PY - 1999/10/26/entrez SP - 1215 EP - 22 JF - Hepatology (Baltimore, Md.) JO - Hepatology VL - 30 IS - 5 N2 - Transforming growth factor-beta1 (TGF-beta1) has been shown to induce apoptosis in normal or transformed hepatocytes. To elucidate the biochemical pathways leading to apoptosis induced by TGF-beta1 in human hepatoma cells (HuH-7), we examined the expression of Bcl-2-related proteins and X-chromosome-linked inhibitor of apoptosis (XIAP), and activation of the caspase cascade following TGF-beta1 treatment. Bcl-xL expression began to decline at 12 hours after TGF-beta1 treatment and progressively decreased to very low levels in a time-dependent manner. Bax expression showed a little change throughout the experiment. On the other hand, activation of caspase-8 was clearly observed at 36 hours after TGF-beta1 treatment, followed by activation of caspase-9, and caspase-3 was activated at 48 hours after treatment at which time apoptosis of HuH-7 cells was observed. TGF-beta1 significantly decreased XIAP expression in HuH-7 cells. Addition of an inhibitor of caspase-8 or caspase-3 (IETD-FMK or DEVD-CHO) markedly inhibited TGF-beta1-induced apoptosis of HuH-7 cells. Fas/Fas ligand (FasL) interactions in HuH-7 cells were not involved in the apoptotic process. Furthermore, epidermal growth factor (EGF) also completely inhibited TGF-beta1-induced apoptosis of HuH-7 cells by inhibiting activation of the caspase cascade. Our results suggested that activation of caspase-3 initiated through caspase-8 activation is involved in the apoptotic process induced by TGF-beta1 in HuH-7 cells. Our results also showed that down-regulation of the expression of Bcl-xL and XIAP by TGF-beta1 may facilitate activation of caspase-3 in these cells. SN - 0270-9139 UR - https://www.unboundmedicine.com/medline/citation/10534343/Activation_of_caspase_8_in_transforming_growth_factor_beta_induced_apoptosis_of_human_hepatoma_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0270913999004814 DB - PRIME DP - Unbound Medicine ER -