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Na + /H + exchange subtype 1 inhibition during extracellular acidification and hypoxia in glioma cells
Author(s) -
Glunde Kristine,
Düßmann Heiko,
Juretschke HansPaul,
Leibfritz Dieter
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.0022-3042.2001.00661.x
Subject(s) - intracellular ph , extracellular , chemistry , biochemistry , intracellular , biophysics , microbiology and biotechnology , biology
Lactacidosis is a common feature of ischaemic brain tissue, but its role in ischaemic neuropathology is still not fully understood. Na + /H + exchange, a mechanism involved in the regulation of intracellular pH (pH i ), is activated by low pH i . The role of Na + /H + 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 + /H + exchanger subtype 1 (NHE‐1). It was compared for normoxia and hypoxia in two glioma cell lines (C6 and F98). pH 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 1 H, 13 C and 31 P NMR spectroscopy of perchloric acid extracts. NHE‐1 contributed to glial pH regulation, especially at pathologically low pH 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.