Na super(+)/H super(+) exchange subtype 1 inhibition during extracellular acidification and hypoxia in glioma cells

• Published in: Journal of neurochemistry Vol. 80; no. 1; pp. 36 - 44
• Main Authors: Glunde, K, Duessmann, H, Juretschke, H-P, Leibfritz, D
• Format: Journal Article
• Language: English
• Published: 01.01.2002
• ISSN: 0022-3042

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.