Calpain is involved in the HIV replication from the latently infected OM10.1 cells
Calpain is involved in the HIV replication from the latently infected OM10.1 cells
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DOI：
10.1016/s0006-291x(03)00447-9
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发表时间：
2003-04-11
影响因子：
3.1
通讯作者：
Okamoto, T
中科院分区：
文献类型：
--
作者：
Teranishi, F;Liu, ZQ;Okamoto, T
用佛波醇酯和钙离子载体（A23187）处理潜伏感染人类免疫缺陷病毒1型（HIV-1）的OM 10.1细胞，可诱导病毒复制，但这种复制可被钙蛋白酶抑制剂1-N-Ac-Leu-Leu-norleucinal（ALLnL）阻断，而不被特异性蛋白酶体抑制剂lactacystin阻断。当纯化的NF-κ B/IkappaB复合物与mu-calpain作用时，通过电泳迁移率变动分析证明了特异性DNA结合活性。μ-钙蛋白酶的这种作用被ALLnL和钙蛋白酶抑制素抑制，而不是被lactacystin抑制。事实上，我们发现μ-钙蛋白酶有效地降解了IkappaB α。此外，我们的蛋白质印迹分析显示，μ-钙蛋白酶在其N-末端和C-末端区域切割IkappaB α，这些区域先前被报道参与与NF-κ B p65的相互作用。这些观察结果表明，在单核细胞/巨噬细胞中，钙信号通过激活钙蛋白酶参与NF-κ B的激活，因此钙蛋白酶抑制剂可能有效抑制潜伏感染的HIV的激活。(C)2003 Elsevier Science（美国）。All rights reserved.
Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor 1, and not by lactacystin, a specific proteasome inhibitor. When the purified NF-kappaB/IkappaB complex was treated with mu-calpain, the specific DNA-binding activity was demonstrated by using electrophoretic mobility shift assay in vitro. This effect of mu-calpain was inhibited by ALLnL and calpastatin and not by lactacystin. In fact, we found that mu-calpain efficiently degraded IkappaBalpha. Furthermore, our Western blotting analysis has revealed that mu-calpain cleaves IkappaBalpha at its N-terminal and C-terminal regions that were previously reported to be involved in the interaction with NF-kappaB p65. These observations indicate that in monocyte/macrophage cells calcium signaling is involved in NF-kappaB activation through activation of calpain and thus calpain inhibitors may be effective in inhibiting the activation of latently infected HIV. (C) 2003 Elsevier Science (USA). All rights reserved.