Tags

Type your tag names separated by a space and hit enter

Insulin and dexamethasone inhibit TGF-beta-induced apoptosis of hepatoma cells upstream of the caspase activation cascade.
Toxicology. 2004 Nov 15; 204(2-3):141-54.T

Abstract

Insulin and dexamethasone are potent inhibitors of apoptosis induced by transforming growth factor-beta1 (TGF-beta) in hepatoma cells. Using FTO-2B rat hepatoma cells, we determined whether the anti-apoptotic effects of these agents result from interference within or upstream of the TGF-beta-induced caspase cascade. Activation of different initiator and effector caspases, Bax and Bcl-xL expression, mitochondrial cytochrome c release and activation of PKB/Akt were analyzed by use of synthetic caspase substrates and Western blotting, respectively. TGF-beta-induced apoptosis was characterized by release of cytochrome c from mitochondria and activation of caspases-3, -7, -8 and -9. These effects were observable as early as 8-12 h after start of treatment and increased with time of observation. Inhibition of TGF-beta-induced apoptosis by insulin and dexamethasone was paralleled by a strong reduction of caspase-3-like activity. Caspase-8 activation was almost completely suppressed by these agents, and caspase-9 activity was decreased to levels within or slightly above unstimulated control cells. In addition, cytochrome c release from mitochondria was efficiently repressed, which was associated with upregulation of Bcl-xL by dexamethasone and activation of PKB/Akt by insulin. Thus, both anti-apoptotic compounds exert their inhibitory effects through modulation of anti-apoptotic signalling pathways involved in regulation of cytochrome c release and activation of the caspase machinery.

Authors+Show Affiliations

Department of Toxicology, Institute of Pharmacology and Toxicology, University of Tübingen, Wilhelmstr. 56, 72074 Tübingen, Germany.No affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15388240

Citation

Wanke, Ines, et al. "Insulin and Dexamethasone Inhibit TGF-beta-induced Apoptosis of Hepatoma Cells Upstream of the Caspase Activation Cascade." Toxicology, vol. 204, no. 2-3, 2004, pp. 141-54.
Wanke I, Schwarz M, Buchmann A. Insulin and dexamethasone inhibit TGF-beta-induced apoptosis of hepatoma cells upstream of the caspase activation cascade. Toxicology. 2004;204(2-3):141-54.
Wanke, I., Schwarz, M., & Buchmann, A. (2004). Insulin and dexamethasone inhibit TGF-beta-induced apoptosis of hepatoma cells upstream of the caspase activation cascade. Toxicology, 204(2-3), 141-54.
Wanke I, Schwarz M, Buchmann A. Insulin and Dexamethasone Inhibit TGF-beta-induced Apoptosis of Hepatoma Cells Upstream of the Caspase Activation Cascade. Toxicology. 2004 Nov 15;204(2-3):141-54. PubMed PMID: 15388240.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Insulin and dexamethasone inhibit TGF-beta-induced apoptosis of hepatoma cells upstream of the caspase activation cascade. AU - Wanke,Ines, AU - Schwarz,Michael, AU - Buchmann,Albrecht, PY - 2004/04/21/received PY - 2004/06/18/revised PY - 2004/06/21/accepted PY - 2004/9/25/pubmed PY - 2004/11/9/medline PY - 2004/9/25/entrez SP - 141 EP - 54 JF - Toxicology JO - Toxicology VL - 204 IS - 2-3 N2 - Insulin and dexamethasone are potent inhibitors of apoptosis induced by transforming growth factor-beta1 (TGF-beta) in hepatoma cells. Using FTO-2B rat hepatoma cells, we determined whether the anti-apoptotic effects of these agents result from interference within or upstream of the TGF-beta-induced caspase cascade. Activation of different initiator and effector caspases, Bax and Bcl-xL expression, mitochondrial cytochrome c release and activation of PKB/Akt were analyzed by use of synthetic caspase substrates and Western blotting, respectively. TGF-beta-induced apoptosis was characterized by release of cytochrome c from mitochondria and activation of caspases-3, -7, -8 and -9. These effects were observable as early as 8-12 h after start of treatment and increased with time of observation. Inhibition of TGF-beta-induced apoptosis by insulin and dexamethasone was paralleled by a strong reduction of caspase-3-like activity. Caspase-8 activation was almost completely suppressed by these agents, and caspase-9 activity was decreased to levels within or slightly above unstimulated control cells. In addition, cytochrome c release from mitochondria was efficiently repressed, which was associated with upregulation of Bcl-xL by dexamethasone and activation of PKB/Akt by insulin. Thus, both anti-apoptotic compounds exert their inhibitory effects through modulation of anti-apoptotic signalling pathways involved in regulation of cytochrome c release and activation of the caspase machinery. SN - 0300-483X UR - https://www.unboundmedicine.com/medline/citation/15388240/Insulin_and_dexamethasone_inhibit_TGF_beta_induced_apoptosis_of_hepatoma_cells_upstream_of_the_caspase_activation_cascade_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0300-483X(04)00346-4 DB - PRIME DP - Unbound Medicine ER -