title: Antimycin A induces apoptosis in As4.1 juxtaglomerular cells.
abstract: Antimycin A, an inhibitor of electron transport in mitochondria, has been used as reactive oxygen species (ROS) generator in the biological system. Here, we investigated the in vitro effect of antimycin A on apoptosis in As4.1 juxtaglomerular cells. Antimycin A efficiently induced apoptosis in As4.1 cells as evidenced by flow cytometric detection of sub-G(1) DNA content, annexin V binding assay and DAPI staining. This apoptotic process was accompanied by loss of mitochondrial transmembrane potential (DeltaPsi(m)), Bcl-2 decrease, caspase-3 activation and PARP cleavage. All of caspase inhibitors tested in this experiment failed to rescue As4.1 cells from antimycin A-induced cell death at the time of 48 h in view of sub-G(1) cells and annexin V positive staining cells. However, with regard to the mitochondrial membrane potential (DeltaPsi(m)), pan caspase inhibitor (Z-VAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) at the concentration of 25 microM noticeably decreased the loss of mitochondrial membrane potential (DeltaPsi(m)) in antimycin A-treated cells. Taken together, we have demonstrated that antimycin A as an inhibitor of electron transport in mitochondria potently induces apoptosis in As4.1 juxtaglomerular cells.
authors.affiliation: Department of Physiology, Medical School, Institute for Medical Sciences, Center for Healthcare Technology Development, Chonbuk National University, JeonJu, Republic of Korea.
authors.forename: Woo-Hyun
authors.initials: WH
authors.lastname: Park
authors.forename: Yong-Whan
authors.initials: YW
authors.lastname: Han
authors.forename: Sang-Wook
authors.initials: SW
authors.lastname: Kim
authors.forename: Suhn-Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Kyung-Woo
authors.initials: KW
authors.lastname: Cho
authors.forename: Sung-Zoo
authors.initials: SZ
authors.lastname: Kim
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D000968:Antimycin A / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D061945:Caspase Inhibitors; D045744:Cell Line, Tumor; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000590:Amino Acid Chloromethyl Ketones; C494827:Bax protein, mouse; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000968:Antimycin A; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3