ACTIVATION OF MULTIPLE PH-REGULATORY PATHWAYS IN GRANULOCYTES BY A PHOSPHOTYROSINE PHOSPHATASE ANTAGONIST

被引:13
作者
BIANCHINI, L [1 ]
NANDA, A [1 ]
WASAN, S [1 ]
GRINSTEIN, S [1 ]
机构
[1] HOSP SICK CHILDREN,DIV CELL BIOL,TORONTO M5G 1X8,ON,CANADA
关键词
D O I
10.1042/bj3010539
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Activated phagocytes undergo a massive burst of metabolic acid generation, yet must be able to maintain their cytosolic pH (pH(i)) within physiological limits. Peroxides of vanadate (V4+-OOH), potent inhibitors of phosphotyrosine phosphatases, have recently been shown to produce activation of the respiratory burst in HL60 granulocytes. We therefore investigated the effects of V4+-OOH on pH(i) homoeostasis in HL60 granulocytes, using a pH-sensitive fluorescent dye. V4+-OOH stimulation induced a biphasic pH change: a transient cytosolic acidification followed by a significant alkalinization. The initial acidification was prevented by inhibition of the NADPH oxidase and was absent in undifferentiated cells lacking oxidase activity. Analysis of the alkalinization phase demonstrated the involvement of the Na+/H+ antiporter, and also provided evidence for activation of two alternative H+-extrusion pathways: a bafilomycin-sensitive component, likely reflecting vacuolar-type H+-ATPase activity, and a Zn2+-sensitive H+-conductive pathway. Our results indicate that V4+-OOH stimulation not only activated the NADPH oxidase but concomitantly stimulated H+-extrusion pathways, enabling the cells to compensate for the massive production of intracellular H+ associated with the respiratory burst.
引用
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页码:539 / 544
页数:6
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