Na super(+)/H super(+) exchange subtype 1 inhibition during extracellular acidification and hypoxia in glioma cells
Lactacidosis is a common feature of ischaemic brain tissue, but its role in ischaemic neuropathology is still not fully understood. Na super(+)/H super(+) exchange, a mechanism involved in the regulation of intracellular pH (pH sub(i)), is activated by low pH sub(i). The role of Na super(+)/H super(...
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Published in | Journal of neurochemistry Vol. 80; no. 1; pp. 36 - 44 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
01.01.2002
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Online Access | Get full text |
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Summary: | Lactacidosis is a common feature of ischaemic brain tissue, but its role in ischaemic neuropathology is still not fully understood. Na super(+)/H super(+) exchange, a mechanism involved in the regulation of intracellular pH (pH sub(i)), is activated by low pH sub(i). The role of Na super(+)/H super(+) exchange subtype 1 was investigated during extracellular acidification and subsequent pH recovery in the absence and presence of (4-isopropyl-3-methylsulphonyl-benzoyl)-guanidine methanesulfonate (HOE642, Cariporid), a new selective and powerful inhibitor of the Na super(+)/H super(+) exchanger subtype 1 (NHE-1). It was compared for normoxia and hypoxia in two glioma cell lines (C6 and F98). pH sub(i) was monitored by fluorescence spectroscopy using the intracellularly trapped pH-sensitive dye 2',7'-bis (carboxyethyl)-5(6)-carboxyfluorescein (BCECF). Alterations in glial cell metabolism were characterized using high-resolution super(1)H, super(13)C and super(31)P NMR spectroscopy of perchloric acid extracts. NHE-1 contributed to glial pH regulation, especially at pathologically low pH sub(i) values. NHE-1 inhibition with HOE642 during acidification caused exacerbated metabolic disorders which were prolonged during extracellular pH recovery. However, NHE-1 inhibition during hypoxia protected the energy state of glial cells. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-1 |
ISSN: | 0022-3042 |