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- W2001509752 abstract "Abstract Ischaemic pre‐conditioning has a powerful protective potential against ischaemia‐induced cell death, and acidosis is an important featur of ischaemia and can lead to apoptosis. Here we tested whether pre‐conditioning with acidosis, that is, acidic pre‐conditioning (APC), may protect coronary endothelial cells (EC) against apoptosis induced by simulated ischaemia. For pre‐conditioning, EC were exposed fo 40 min. to acidosis (pH 6.4) followed by a 14‐hrs recovery period (pH 7.4) and finally treated for 2 hrs with simulated ischaemia (glucose‐free anoxia at pH 6.4). Cells undergoing apoptosis were visualized by chromatin staining or by determination of caspase‐3 activit Simulated ischaemia in untreated EC increased caspase‐3 activity and the number of apoptotic cell (31.3 ± 1.3% versus 3.9 ± 0.6% in control). APC significantly reduced the rate of apoptosis (14.2 ± 1.3%) and caspase‐3 activity. Western blot analysis exploring the under lying mechanism leading to this protection revealed suppression of the endoplasmic reticulum‐ (reduced cleavage of caspase‐12) and mitochondria‐mediated (reduced cytochrome C release) pathways of apoptosis. These effects were associated with an over‐expression of the anti‐apoptotic protein Bcl‐xL 14 hrs after APC, whereas no effect on the expression of Bcl‐2, Bax, Bak, procaspase‐12, reticulum‐localized chaperones (GRP78, calreticulin), HSP70, HSP32 and HSP27 could be detected. Knock‐down of Bcl‐xL by siRNA‐treatment prevented the protective effect of APC. In conclusion, short acidic pre‐treatment can protect EC against ischaemic apoptosis. The mechanism of this protection consists of suppression of the endoplasmic reticulum‐ and mitochondria‐mediated pathways. Over‐expression of the anti apoptotic protein Bcl‐xL is responsible for the increased resistance to apoptosis during ischaemic insult." @default.
- W2001509752 created "2016-06-24" @default.
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- W2001509752 date "2008-09-01" @default.
- W2001509752 modified "2023-10-16" @default.
- W2001509752 title "Acidic pre-conditioning suppresses apoptosis and increases expression of Bcl-xL in coronary endothelial cells under simulated ischaemia" @default.
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- W2001509752 doi "https://doi.org/10.1111/j.1582-4934.2007.00172.x" @default.
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