Tanaka Y, Yoshihara K, Kojima K, Itaya A, Kameoka M, Ikuta K, Kamiya T
Department of Biochemistry, Nara Medical University, Japan.
Biochem Biophys Res Commun. 1995 Aug 4;213(1):161-8. doi: 10.1006/bbrc.1995.2111.
Poly(ADP-ribose) polymerase, a nuclear enzyme, is suggested to be involved in apoptotic cell death. It is also known that apoptotic cell death following HIV-1 infection is the most important feature of AIDS pathogenesis. Thus, to evaluate the relations between the enzyme and HIV-1 infection, we examined the enzyme activity of several subclones of human promonocytic cell line U937, which showed different susceptibility to HIV-1 infection. The nuclear extracts of two "high type clones" (possessing high susceptibility to HIV-1 infection) contained approximately 4 to 7-fold less enzyme than two low type clones when assayed under a full activation of enzyme. Parent clone, possessing an intermediate susceptibility to HIV-1, showed an intermediate enzyme level, suggesting that low level of this enzyme in cells is important for an effective infection of HIV-1. Furthermore, when these U937 subclones persistently infected with HIV-1 were examined, a dramatic decrease of the enzyme activity, reaching 2 to 16% of uninfected cells, was observed in all of these clones. The levels of poly(ADP-ribose) glycohydrolase in these clones were relativity unchanged. Activity gel analysis and immunoblotting of the enzyme in the clones revealed that the low enzyme activities observed in uninfected "high type clones" and all HIV-1-infected clones were due to a marked decrease of the enzyme protein itself. All of these results suggest that HIV-1 infection involves some mechanism to downregulate cellular poly(ADP-ribose) polymerase and that a lower level of the enzyme may be essential for an effective production of the virus and/or for a stable virus/host interaction.
聚（ADP - 核糖）聚合酶是一种核酶，被认为与凋亡性细胞死亡有关。众所周知，HIV - 1感染后的凋亡性细胞死亡是艾滋病发病机制的最重要特征。因此，为了评估该酶与HIV - 1感染之间的关系，我们检测了人原单核细胞系U937的几个亚克隆的酶活性，这些亚克隆对HIV - 1感染表现出不同的易感性。在酶完全激活的条件下进行检测时，两个“高易感性克隆”（对HIV - 1感染具有高易感性）的核提取物中该酶的含量比两个低易感性克隆少约4至7倍。对HIV - 1具有中等易感性的亲本克隆显示出中等水平的酶，这表明细胞中该酶的低水平对于HIV - 1的有效感染很重要。此外，当检测这些持续感染HIV - 1的U937亚克隆时，在所有这些克隆中均观察到酶活性急剧下降，降至未感染细胞的2%至16%。这些克隆中聚（ADP - 核糖）糖苷水解酶的水平相对未变。对克隆中的该酶进行活性凝胶分析和免疫印迹显示，在未感染的“高易感性克隆”和所有HIV - 1感染的克隆中观察到的低酶活性是由于酶蛋白本身的显著减少。所有这些结果表明，HIV - 1感染涉及某种下调细胞聚（ADP - 核糖）聚合酶的机制，并且较低水平的该酶可能对于病毒的有效产生和/或稳定的病毒/宿主相互作用至关重要。
