Modulation of microglial superoxide production by α-tocopherol in vitro:: attenuation of p67phox translocation by a protein phosphatase-dependent pathway

被引:39
作者
Egger, T
Hammer, A
Wintersperger, A
Goti, D
Malle, E
Sattler, W
机构
[1] Graz Univ, Inst Med Biochem & Mol Biol, A-8010 Graz, Austria
[2] Graz Univ, Inst Histol & Embryol, A-8010 Graz, Austria
关键词
BV-2; cells; microglia; NADPH-oxidase; p67(phox); respiratory burst; vitamin E;
D O I
10.1046/j.1471-4159.2001.00641.x
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
As in other phagocytic cells, the NADPH-oxidase system in microglia is thought to be primarily responsible for the production of superoxide anion radicals (O-2(-).), a potentially cytotoxic reactive oxygen species. The assembly of a functional NADPH-oxidase complex at the plasma membrane depends on the phosphorylation and subsequent translocation of several cytosolic subunits. Immunocytochemical and subcellular fractionation experiments performed during the present study revealed that the NADPH-oxidase subunit P67(phox) translocates from the cytosol to the plasma membrane upon stimulation. Pre-incubation of microglia in a-tocopherol (alpha TocH) containing medium decreased O-2(-). production in a time- and concentration-dependent manner, findings attributed to attenuated p67(phox) translocation to the plasma membrane. Moreover, alpha TocH-supplementation of the culture medium resulted in decreased microglial protein kinase C (PKC) activities, an effect that could be partially or completely reversed by the addition of protein phosphatase inhibitors (okadaic acid and calyculin A). The addition of the PKC-inhibitor staurosporine inhibited the microglial respiratory burst in a manner comparable to alpha TocH. The addition of okadaic acid or calyculin A completely restored O-2(-). production in alpha TocH-supplemented cells. The present findings suggest that alpha TocH inactivates PKC via a PP1 or PP2A-mediated pathway and, as a consequence, blocks the phosphorylation-dependent translocation of p67(phox) to the plasma membrane. As a result, O-2(-). production by the microglial NADPH-oxidase system is substantially inhibited.
引用
收藏
页码:1169 / 1182
页数:14
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