Nitric oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release

• Verfasst von: Ushmorov, Alexey [VerfasserIn]
• Verfasst von: Ratter, Frank [VerfasserIn]
• Verfasst von: Lehmann, Volker [VerfasserIn]
• Verfasst von: Dröge, Wulf [VerfasserIn]
• Verfasst von: Schirrmacher, Volker [VerfasserIn]
• Verfasst von: Umansky, Viktor [VerfasserIn]
• Titel: Nitric oxide-induced apoptosis in human leukemic lines requires mitochondrial lipid degradation and cytochrome C release
• Verf.angabe: by Alexey Ushmorov, Frank Ratter, Volker Lehmann, Wulf Dröge, Volker Schirrmacher, and Victor Umansky
• E-Jahr: 1999
• Jahr: April 1, 1999
• Umfang: 11 S.
• Fussnoten: Gesehen am 20.02.2019 ; Der Vorname von Viktor Umansky ist in der Verfasserangabe falsch geschrieben
• Titel Quelle: Enthalten in: Blood
• Ort Quelle: Washington, DC : American Society of Hematology, 1946
• Jahr Quelle: 1999
• Band/Heft Quelle: 93(1999), 7, Seite 2342-2352
• ISSN Quelle: 1528-0020
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1587834057

Abstract

We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.