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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 354750.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Importance of bicarbonate transport for ischaemia-induced apoptosis of coronary endothelial cells
Authors:Kumar, S.; Kasseckert, S.; Kostin, S.; Abdallah, Y.; Piper, H. M.; Steinhoff, G.; Reusch, H. P.; Ladilov, Y.
Journal Abbrev.:J Cell Mol Med
Issue / Number:4
Start Page:798
End Page:809
Audience:Not Specified
Abstract / Description:Bicarbonate transport (BT) has been previously shown to participate in apoptosis induced by various stress factors. However, the precise role of BT in ischaemia-induced apoptosis is still unknown. To investigate this subject, rat coronary endothelial cells (EC) were exposed to simulated ischaemia (glucose free anoxia at Ph 6.4) for 2 hrs and cells undergoing apoptosis were visualized by nuclear staining or by determination of cas-pase- 3 activity. To inhibit BT, EC were either treated with the inhibitor of BT 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS, 300 mumol/l) or exposed to ischaemia in bicarbonate free, 4-(2-hydroxyethyl)-I-piperazi-neethanesulphonic acid (HEPES)-buffered medium. Simulated ischaemia in bicarbonate-buffered medium (Bic) increased caspase-3 activity and the number of apoptotic cell (23.7 + 1.4%versus 5.1 + 1.2% in control). Omission of bicarbonate during ischaemia further significantly increased caspase-3 activity and the number of apoptotic cells (36.7 1.7%). Similar proapoptotic effect was produced by DIDS treatment during ischaemia in Bic, whereas DIDS had no effect when applied in bicarbonate-free, HEPES-buffered medium (Hep). Inhibition of BT was without influence on cytosolic acidification during ischaemia and slightly reduced cytosolic Ca(2+) accumulation. Initial characterization of the underlying mechanism leading to apoptosis induced by BT inhibition revealed activation of the mitochondrial pathway of apoptosis, i.e., increase of cytochrome C release, depolarization of mitochondria and translocation of Bax protein to mitochondria. In contrast, no activation of death receptor-dependent pathway (caspase-8 cleavage) and endoplasmic reticulum- dependent pathway (caspase-12 cleavage) was detected. In conclusion, BT plays an important role in ischaemia-induced apoptosis of coronary EC by suppression of mitochondria-dependent apoptotic pathway.
Free Keywords:Acidosis; Animals; *Apoptosis; Bicarbonates/*metabolism; Biological Transport; Calcium/metabolism; Caspase 12/metabolism; Caspase 3/metabolism; Cell Hypoxia; Cytochromes c/secretion; Cytosol/pathology; Endothelial Cells/enzymology/*metabolism/*pathology; Hydrogen-Ion Concentration; Male; Membrane Potential, Mitochondrial; Mitochondria; Myocardial Ischemia/*metabolism; Rats; Rats, Wistar; Time Factors; bcl-2-Associated X Protein/metabolism
Comment of the Author/Creator:Date: 2007, Jul-Aug
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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