HIV type 1 Tat protein is a survival factor for Kaposi's sarcoma and endothelial cells
HIV type 1 Tat protein is a survival factor for Kaposi's sarcoma and endothelial cells
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DOI：
10.1089/088922201750290087
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发表时间：
2001-07-01
影响因子：
1.5
通讯作者：
Camussi, G
中科院分区：
文献类型：
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作者：
Cantaluppi, V;Biancone, L;Camussi, G
HIV-1 Tat蛋白与艾滋病相关的卡波西肉瘤（KS）的发病机制有直接关系；然而，其对KS纺锤形和内皮细胞凋亡的影响在很大程度上尚未被探索。由于细胞凋亡易感性与肿瘤的发展和对治疗的反应有关，我们研究了Tat对KS和内皮细胞凋亡存活的影响。Tat的作用在三个KS细胞系（KS-imm， KS- c1和KS- l3）暴露于化疗药物长春新碱（目前用于治疗该肿瘤），以及通过血清停药诱导发生凋亡的人脐静脉源性内皮细胞（HUVECs）中进行了评估。通过酶促测定、显微镜检查染色质和细胞骨架、评估质膜完整性和亚二倍体DNA含量、TUNEL测定和测量caspase-3活性来评估细胞凋亡。以剂量依赖的方式，分别保护三种KS细胞系和HUVECs免受长春新碱或血清饥饿诱导的凋亡。这种影响似乎与Fas、Bcl-2或Bax表达的调节无关。相反，在长春新碱处理的KS细胞中，Tat上调Bcl-X-L的表达，并诱导caspase-3活性相应降低。综上所述，这些结果表明HIV-1 Tat蛋白可能通过维持内皮细胞和转化细胞的存活来影响KS的发生和进展。
The HIV-1 Tat protein has been directly implicated in the pathogenesis of AIDS-related Kaposi's sarcoma (KS); however, its effects on KS spindle-shaped and endothelial cell apoptosis are largely unexplored. Since susceptibility to apoptosis is relevant for tumor development and response to therapy, we investigated the effects of Tat on KS and endothelial cell survival from apoptosis. The effect of Tat was evaluated in three KS cell lines (KS-imm, KS-C1, and KS-L3) exposed to the chemotherapy agent vincristine, currently used for the treatment of this tumor, and in human umbilical vein-derived endothelial cells (HUVECs) induced to undergo apoptosis by serum withdrawal. Apoptosis was assessed by enzymatic assays, microscopic examination of chromatin and cytoskeleton, evaluation of plasma membrane integrity and subdiploid DNA content, TUNEL assays, and measurement of caspase-3 activity. Tat, in a dose-dependent manner, protected the three KS cell lines and HUVECs from apoptosis induced by vincristine or serum starvation, respectively. This effect appeared to be independent of modulation of Fas, Bcl-2, or Bax expression. In contrast, Tat upregulated Bcl-X-L expression and induced a relevant decrease in caspase-3 activity in vincristine-treated KS cells. Taken together, these results suggest that the HIV-1 Tat protein may factor KS development and progression by sustaining endothelial and transformed cell survival.