Change in intracellular pH causes the toxic Ca2+ entry via NCX1 in neuron- and glia-derived cells.
Brain hypoxia or ischemia causes acidosis and the intracellular accumulation of Ca(2+) in neuron. The aims of the present study were to elucidate the interaction between intracellular pH and Ca(2+) during transient acidosis and its effects on the viability of neuronal and glial cells. Intracellular Ca(2+) and pH were measured using the fluorescence of fura-2 and 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein acetoxymethyl ester in neuroblastoma (IMR-32), glioblastoma (T98G), and astrocytoma (CCF-STTG1) cell lines. The administration of 5 mM propionate caused intracellular acidification in IMR-32 and T98G cells but not in CCF-STTG1 cells. After the removal of propionate, the intracellular pH recovered to the resting level. The intracellular Ca(2+) transiently increased upon the removal of propionate in IMR-32 and T98G cells but not in CCF-STTG1 cells. The transient Ca(2+) increase caused by the withdrawal of intracellular acidification was abolished by the removal of external Ca(2+), diminished by a reduction of external Na(+), and inhibited by benzamil. Transient acidosis caused cell death, whereas the cells were more viable in the absence of external Ca(2+). Benzamil alleviated cell death caused by transient acidosis in IMR-32 and T98G cells but not in CCF-STTG1 cells. These results suggest that recovery from intracellular acidosis causes a transient increase in cytosolic Ca(2+) due to reversal of Ca(2+) transport via Na(+)/Ca(2+) exchanger coactivated with Na(+)/H(+) exchanger, which can cause cell death.
Shono
Yuji
Y
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka, 812-8582, Japan.
Kamouchi
Masahiro
M
Kitazono
Takanari
T
Kuroda
Junya
J
Nakamura
Kuniyuki
K
Hagiwara
Noriko
N
Ooboshi
Hiroaki
H
Ibayashi
Setsuro
S
Iida
Mitsuo
M
D000138:Acidosis / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003600:Cytosol / Q000378:metabolism; D045604:Extracellular Fluid / Q000378:metabolism; D005456:Fluorescent Dyes; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000503:physiopathology; D009410:Nerve Degeneration / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D009457:Neuroglia / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D011422:Propionates / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism; D019831:Sodium-Calcium Exchanger / Q000378:metabolism*
D005456:Fluorescent Dyes; D011422:Propionates; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1; C013407:benzamil; D000584:Amiloride; D012964:Sodium; C029658:propionic acid; D002118:Calcium