Tags

Type your tag names separated by a space and hit enter

Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells.
Am J Physiol Gastrointest Liver Physiol. 2005 Oct; 289(4):G731-8.AJ

Abstract

This study was undertaken to determine whether the Bcl-2 family proteins and Smac are regulators of aspirin-mediated apoptosis in a gastric mucosal cell line known as AGS cells. Cells were incubated with varying concentrations of acetylsalicylic acid (ASA; 2-40 mM), with or without preincubation of caspase inhibitors. Apoptosis was characterized by Hoechst staining and DNA-histone-associated complex formation. Antiapoptotic Bcl-2, proapoptotic Bax and Bid, Smac, and cytochrome-c oxidase (COX IV) were analyzed by Western blot analyses from cytosol and mitochondrial fractions. ASA downregulated Bcl-2 protein expression and induced Bax translocation into the mitochondria and cleavage of Bid. In contrast, expression of Smac was significantly decreased in mitochondrial fractions of ASA-treated cells. Bax and Bid involvement in apoptosis regulation was dependent on caspase activation, because caspase-8 inhibition suppressed Bax translocation and Bid processing. Caspase-9 inhibition prevented Smac release from mitochondria. Additionally, increased expression of the oxidative phosphorylation enzyme COX IV was observed in mitochondrial fractions exposed to ASA at concentrations >5 mM. Although caspase-8 inhibition had no effect on aspirin-induced apoptosis and DNA-histone complex formation, caspase-9 inhibition significantly decreased both of these events. We conclude that Bcl-2 protein family members and Smac regulate the apoptotic pathway in a caspase-dependent manner. Our results indicate also that mitochondrial integration and oxidative phosphorylation play a critical role in the pathogenesis of apoptosis in human gastric epithelial cells.

Authors+Show Affiliations

Dept. of Surgery, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, VA 23298-0568, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15976387

Citation

Redlak, Maria J., et al. "Role of Mitochondria in Aspirin-induced Apoptosis in Human Gastric Epithelial Cells." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 289, no. 4, 2005, pp. G731-8.
Redlak MJ, Power JJ, Miller TA. Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2005;289(4):G731-8.
Redlak, M. J., Power, J. J., & Miller, T. A. (2005). Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. American Journal of Physiology. Gastrointestinal and Liver Physiology, 289(4), G731-8.
Redlak MJ, Power JJ, Miller TA. Role of Mitochondria in Aspirin-induced Apoptosis in Human Gastric Epithelial Cells. Am J Physiol Gastrointest Liver Physiol. 2005;289(4):G731-8. PubMed PMID: 15976387.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Role of mitochondria in aspirin-induced apoptosis in human gastric epithelial cells. AU - Redlak,Maria J, AU - Power,Jacinda J, AU - Miller,Thomas A, Y1 - 2005/06/23/ PY - 2005/6/25/pubmed PY - 2005/10/28/medline PY - 2005/6/25/entrez SP - G731 EP - 8 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 289 IS - 4 N2 - This study was undertaken to determine whether the Bcl-2 family proteins and Smac are regulators of aspirin-mediated apoptosis in a gastric mucosal cell line known as AGS cells. Cells were incubated with varying concentrations of acetylsalicylic acid (ASA; 2-40 mM), with or without preincubation of caspase inhibitors. Apoptosis was characterized by Hoechst staining and DNA-histone-associated complex formation. Antiapoptotic Bcl-2, proapoptotic Bax and Bid, Smac, and cytochrome-c oxidase (COX IV) were analyzed by Western blot analyses from cytosol and mitochondrial fractions. ASA downregulated Bcl-2 protein expression and induced Bax translocation into the mitochondria and cleavage of Bid. In contrast, expression of Smac was significantly decreased in mitochondrial fractions of ASA-treated cells. Bax and Bid involvement in apoptosis regulation was dependent on caspase activation, because caspase-8 inhibition suppressed Bax translocation and Bid processing. Caspase-9 inhibition prevented Smac release from mitochondria. Additionally, increased expression of the oxidative phosphorylation enzyme COX IV was observed in mitochondrial fractions exposed to ASA at concentrations >5 mM. Although caspase-8 inhibition had no effect on aspirin-induced apoptosis and DNA-histone complex formation, caspase-9 inhibition significantly decreased both of these events. We conclude that Bcl-2 protein family members and Smac regulate the apoptotic pathway in a caspase-dependent manner. Our results indicate also that mitochondrial integration and oxidative phosphorylation play a critical role in the pathogenesis of apoptosis in human gastric epithelial cells. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/15976387/Role_of_mitochondria_in_aspirin_induced_apoptosis_in_human_gastric_epithelial_cells_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00150.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -