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Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP.
Cell Death Differ 2006; 13(3):512-23CD

Abstract

Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-alpha plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression.

Authors+Show Affiliations

Vascular System Research Center, College of Medicine, Kangwon National University, Chunchon, Kangwon-Do, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16167066

Citation

Oh, H-Y, et al. "Dexamethasone Protects Primary Cultured Hepatocytes From Death Receptor-mediated Apoptosis By Upregulation of CFLIP." Cell Death and Differentiation, vol. 13, no. 3, 2006, pp. 512-23.
Oh HY, Namkoong S, Lee SJ, et al. Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP. Cell Death Differ. 2006;13(3):512-23.
Oh, H. Y., Namkoong, S., Lee, S. J., Por, E., Kim, C. K., Billiar, T. R., ... Kim, Y. M. (2006). Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP. Cell Death and Differentiation, 13(3), pp. 512-23.
Oh HY, et al. Dexamethasone Protects Primary Cultured Hepatocytes From Death Receptor-mediated Apoptosis By Upregulation of CFLIP. Cell Death Differ. 2006;13(3):512-23. PubMed PMID: 16167066.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dexamethasone protects primary cultured hepatocytes from death receptor-mediated apoptosis by upregulation of cFLIP. AU - Oh,H-Y, AU - Namkoong,S, AU - Lee,S-J, AU - Por,E, AU - Kim,C-K, AU - Billiar,T R, AU - Han,J-A, AU - Ha,K-S, AU - Chung,H-T, AU - Kwon,Y-G, AU - Lee,H, AU - Kim,Y-M, PY - 2005/9/17/pubmed PY - 2006/4/21/medline PY - 2005/9/17/entrez SP - 512 EP - 23 JF - Cell death and differentiation JO - Cell Death Differ. VL - 13 IS - 3 N2 - Dexamethasone (DEX) pretreatment protected hepatocytes from TNF-alpha plus actinomycin D (ActD)-induced apoptosis by suppressing caspase-8 activation and the mitochondria-dependent apoptosis pathway. DEX treatment upregulated cellular FLICE inhibitory protein (cFLIP) expression, but did not alter the protein levels of Bcl-2, Bcl-xL, Mcl-1, and cIAP as well as Akt activation. The increased cFLIP mRNA level by DEX was inhibited by ActD, indicating that DEX upregulates cFLIP expression at the transcriptional step. DEX also inhibited Jo2-mediated hepatocyte apoptosis by blocking the formation of the death-inducing signaling complex and caspase-8 activation. Specific downregulation of cFLIP expression using siRNA reversed the antiapoptotic effect of DEX by increasing caspase-8 activation. Moreover, DEX administration into mice increased cFLIP expression in the liver and prevented Jo2-induced hepatic injury by inhibiting caspase-8 and -3 activities. Our results indicate that DEX exerts a protective role in death receptor-induced in vitro and in vivo hepatocyte apoptosis by upregulating cFLIP expression. SN - 1350-9047 UR - https://www.unboundmedicine.com/medline/citation/16167066/Dexamethasone_protects_primary_cultured_hepatocytes_from_death_receptor_mediated_apoptosis_by_upregulation_of_cFLIP_ L2 - http://dx.doi.org/10.1038/sj.cdd.4401771 DB - PRIME DP - Unbound Medicine ER -