J Liu, C Xu, L Chen, P Xu, H Xiong
Index: Cell Death Dis. 3 , e254, (2012)
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Inflammatory responses mediated by activated microglia play a pivotal role in the pathogenesis of human immunodeficiency virus type 1 (HIV-1)-associated neurocognitive disorders. Studies on identification of specific targets to control microglia activation and resultant neurotoxic activity are imperative. Increasing evidence indicate that voltage-gated K(+) (K(v)) channels are involved in the regulation of microglia functionality. In this study, we investigated K(v)1.3 channels in the regulation of neurotoxic activity mediated by HIV-1 glycoprotein 120 (gp120)-stimulated rat microglia. Our results showed treatment of microglia with gp120 increased the expression levels of K(v)1.3 mRNA and protein. In parallel, whole-cell patch-clamp studies revealed that gp120 enhanced microglia K(v)1.3 current, which was blocked by margatoxin, a K(v)1.3 blocker. The association of gp120 enhancement of K(v)1.3 current with microglia neurotoxicity was demonstrated by experimental results that blocking microglia K(v)1.3 attenuated gp120-associated microglia production of neurotoxins and neurotoxicity. Knockdown of K(v)1.3 gene by transfection of microglia with K(v)1.3-siRNA abrogated gp120-associated microglia neurotoxic activity. Further investigation unraveled an involvement of p38 MAPK in gp120 enhancement of microglia K(v)1.3 expression and resultant neurotoxic activity. These results suggest not only a role K(v)1.3 may have in gp120-associated microglia neurotoxic activity, but also a potential target for the development of therapeutic strategies.
Structure | Name/CAS No. | Molecular Formula | Articles |
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Margatoxin
CAS:145808-47-5 |
C178H286N52O50S7 |
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2012-05-03 [J. Phys. Chem. B 116(17) , 5132-40, (2012)] |
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Potassium secretion by voltage-gated potassium channel Kv1.3...
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Pharmacological inhibition of Kv1.3 fails to modulate insuli...
2011-08-01 [Am. J. Physiol. Endocrinol. Metab. 301(2) , E380-90, (2011)] |
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