Tags

Type your tag names separated by a space and hit enter

Down-regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death.
Biochem Biophys Res Commun. 2002 Feb 01; 290(4):1275-81.BB

Abstract

The anti-apoptotic effect of a chloride-bicarbonate exchange blocker has been previously examined in endothelial cells and cardiomyocytes. However, the anti-apoptotic effects of this blocker on epithelial cells and the mechanism of the anti-apoptotic effect remain unknown. We examined the anti-apoptotic effects of a chloride-bicarbonate exchange blocker in a renal epithelial cell line (MDCK cells). Changes in the expression of bcl-2 family proteins, which are known to have anti-apoptotic effects, were also examined. Staurosporine was used to induce apoptotic cell death in the MDCK cells. Staurosporine treatment was sufficient to induce apoptotic cell death, detected by propidium iodide and DNA ladder formation. A chloride-bicarbonate exchange blocker was added 24 h before the staurosporine treatment and during treatment. The chloride-bicarbonate exchange blocker inhibited the staurosporine-induced apoptosis in the MDCK cells in a dose-dependent manner. The expression of bcl-2 family gene products was detected by RT-PCR and Western blotting. No changes in the expression of Bax, Bid and Bik (pro-apoptotic proteins), or Bcl-2 (an anti-apoptotic protein) were detected. However, Mcl-1 expression was reduced by the staurosporine treatment, and this reduction was recovered when the chloride-bicarbonate exchange blocker was added. LY294002, a PI 3-kinase inhibitor, partially inhibited this anti-apoptotic effect. In conclusion, chloride-bicarbonate exchange blockers appear to offer cell-protective effects via Mcl-1 up-regulation.

Authors+Show Affiliations

Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan.No 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

11812001

Citation

Araki, Takashi, et al. "Down-regulation of Mcl-1 By Inhibition of the PI3-K/Akt Pathway Is Required for Cell Shrinkage-dependent Cell Death." Biochemical and Biophysical Research Communications, vol. 290, no. 4, 2002, pp. 1275-81.
Araki T, Hayashi M, Watanabe N, et al. Down-regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death. Biochem Biophys Res Commun. 2002;290(4):1275-81.
Araki, T., Hayashi, M., Watanabe, N., Kanuka, H., Yoshino, J., Miura, M., & Saruta, T. (2002). Down-regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death. Biochemical and Biophysical Research Communications, 290(4), 1275-81.
Araki T, et al. Down-regulation of Mcl-1 By Inhibition of the PI3-K/Akt Pathway Is Required for Cell Shrinkage-dependent Cell Death. Biochem Biophys Res Commun. 2002 Feb 1;290(4):1275-81. PubMed PMID: 11812001.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Down-regulation of Mcl-1 by inhibition of the PI3-K/Akt pathway is required for cell shrinkage-dependent cell death. AU - Araki,Takashi, AU - Hayashi,Matsuhiko, AU - Watanabe,Naohide, AU - Kanuka,Hirotaka, AU - Yoshino,Jun, AU - Miura,Masayuki, AU - Saruta,Takao, PY - 2002/1/29/pubmed PY - 2002/3/13/medline PY - 2002/1/29/entrez SP - 1275 EP - 81 JF - Biochemical and biophysical research communications JO - Biochem Biophys Res Commun VL - 290 IS - 4 N2 - The anti-apoptotic effect of a chloride-bicarbonate exchange blocker has been previously examined in endothelial cells and cardiomyocytes. However, the anti-apoptotic effects of this blocker on epithelial cells and the mechanism of the anti-apoptotic effect remain unknown. We examined the anti-apoptotic effects of a chloride-bicarbonate exchange blocker in a renal epithelial cell line (MDCK cells). Changes in the expression of bcl-2 family proteins, which are known to have anti-apoptotic effects, were also examined. Staurosporine was used to induce apoptotic cell death in the MDCK cells. Staurosporine treatment was sufficient to induce apoptotic cell death, detected by propidium iodide and DNA ladder formation. A chloride-bicarbonate exchange blocker was added 24 h before the staurosporine treatment and during treatment. The chloride-bicarbonate exchange blocker inhibited the staurosporine-induced apoptosis in the MDCK cells in a dose-dependent manner. The expression of bcl-2 family gene products was detected by RT-PCR and Western blotting. No changes in the expression of Bax, Bid and Bik (pro-apoptotic proteins), or Bcl-2 (an anti-apoptotic protein) were detected. However, Mcl-1 expression was reduced by the staurosporine treatment, and this reduction was recovered when the chloride-bicarbonate exchange blocker was added. LY294002, a PI 3-kinase inhibitor, partially inhibited this anti-apoptotic effect. In conclusion, chloride-bicarbonate exchange blockers appear to offer cell-protective effects via Mcl-1 up-regulation. SN - 0006-291X UR - https://www.unboundmedicine.com/medline/citation/11812001/Down_regulation_of_Mcl_1_by_inhibition_of_the_PI3_K/Akt_pathway_is_required_for_cell_shrinkage_dependent_cell_death_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006291X02963291 DB - PRIME DP - Unbound Medicine ER -