کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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4319718 | 1290828 | 2008 | 5 صفحه PDF | دانلود رایگان |
Calcineurin is a Ca2+/calmodulin-dependent protein phosphatase expressed at high levels in brain. Many electrophysiological and pharmacological findings have shown that calcineurin plays an important role in brain function. FK506 is always used as a specific calcineurin inhibitor in these researches. But these reports did not quantify the calcineurin activity in FK506-treated brain. Here we first investigated the inhibitory effect of FK506 injected into the mouse brain ventricle on CN activity. FK506 reduced calcineurin activity in a dose-dependent manner, without affecting its amount. Injection of 12.5 nmol FK506 also significantly enhanced the phosphorylation of tau at Ser-262 (12E8 site), Ser-198, Ser-199, and/or Ser-202 (Tau-1 site) and Ser-396 and/or Ser-404 (PHF-1 site), without affecting total tau. It is suggested that calcineurin plays an important role in tau phosphorylation, dependently of its activity. Compared with the effects of cyclosporin A, another specific inhibitor of CN in our previous study, we first evaluate that such infusion of FK506 is more effective than that of cyclosporin A on calcineurin inhibition and tau phosphorylation.
Journal: Brain Research Bulletin - Volume 76, Issue 5, 30 July 2008, Pages 464–468