Acidic preconditioning protects endothelial cells against apoptosis through p38- and Akt-dependent Bcl-xL overexpression.

Abstract

To analyze the underlying cellular mechanisms of adaptation to ischemia-induced apoptosis through short acidic pretreatment, i.e. acidic preconditioning (APC), Wistar rat coronary endothelial cells (EC) were exposed for 40 min to acidosis (pH 6.4) followed by a 14 h recovery period (pH 7.4) and finally treated for 2 h with simulated in vitro ischemia (glucose-free anoxia at pH 6.4). APC led to a transient activation of p38 and Akt kinases, but not of JNK and ERK1/2 kinases, which was accompanied by significant reduction of the apoptotic cell number, caspase-12/-3 cleavage and Bcl-xL overexpression. These effects of APC were completely abolished by prevention of Akt- or p38-phosphorylation during APC. Furthermore, knock-down of Bcl-xL by siRNA-transfection also abolished the anti-apoptotic effect of APC. Therefore, APC leads to protection of EC against ischemic apoptosis by activation of Akt and p38 followed by overexpression of Bcl-xL, which is a key anti-apoptotic mechanism of APC.

• Authors: Jan-Paul Flacke, Sanjeev Kumar, Sawa Kostin, H Peter Reusch, Yury Ladilov
• Journal: Apoptosis : an international journal on programmed cell death (Apoptosis) Vol. 14 Issue 1 Pg. 90-6 (Jan 2009) ISSN: 1573-675X [Electronic] Netherlands
• PMID: 19082728 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• RNA, Small Interfering
• bcl-X Protein
• Proto-Oncogene Proteins c-akt
• p38 Mitogen-Activated Protein Kinases
• Caspase 12

Topics

• Animals
• Apoptosis
• Caspase 12 (metabolism)
• Endothelial Cells (enzymology)
• Gene Expression Regulation, Enzymologic
• Hydrogen-Ion Concentration
• Ischemic Preconditioning
• Male
• Proto-Oncogene Proteins c-akt (metabolism)
• RNA, Small Interfering (metabolism)
• Rats
• Rats, Wistar
• Time Factors
• bcl-X Protein (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)