Alkaline stress-induced apoptosis in human pulmonary artery endothelial cells.

Full Abstract

The effect of alkaline stress, or an increase in extracellular pH (pHext), on cell viability is poorly defined. Human pulmonary artery endothelial cells (HPAEC) were subjected to alkaline stress using different methods of increasing pHext. Viability and mode of cell death following alkaline stress were determined by assessing nuclear morphology, ultrastructural features, and caspase-3 activity. Incubation of monolayers in media set to different pHext values (7.4-8.4) for 24-h induced morphological changes suggesting apoptosis (35-45% apoptotic cells) following severe alkaline stress. The magnitude of apoptosis was related to the severity of alkaline stress. These findings were confirmed with an assessment of ultrastructural changes and caspase-3 activation. While there was no difference in the intracellular calcium level ([Ca(2+)](i)) in monolayers set to pHext 7.4 versus 8.4 following the first hour of alkaline stress, blockade of calcium uptake with the chelator, EGTA, potentiated the magnitude of apoptosis under these conditions. Potentiation of apoptosis was reduced by calcium supplementation of the media. Finally, alkaline stress was associated with an increase in intracellular pH. This is the first report of apoptosis following alkaline stress in endothelial cells in the absence of other cell death stimuli.

Author information

Author/s: Cutaia, M (M); Black, A D (AD); Cohen, I (I); Cassai, N D (ND); Sidhu, G S (GS);

Affiliation: Pulmonary Disease Section, Department of Medicine, Veterans Administration Medical Center, Brooklyn Campus, SUNY/Downstate Health Sciences Center, Brooklyn, NY 11209-7104, USA. michael.cutaia(-atsign-)med.va.gov

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.

Journal: Apoptosis : an international journal on programmed cell death (Apoptosis), published in United States. (Language: eng)

Reference: 2005-Dec; vol 10 (issue 6) : pp 1457-67

Dates: Created 2006/01/23; Completed 2008/03/25;

PMID: 16215687, status: MEDLINE (last retrieved date: 2/18/2009)

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