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R5 HIV-1 gp120 Activates p38 MAPK to Induce Rat Cardiomyocyte Injury by the CCR5 Coreceptor
Pathobiology ( IF 5 ) Pub Date : 2019-01-01 , DOI: 10.1159/000502238
Rui Gao 1, 2 , Qiujuan Fang 3 , Xi Zhang 4 , Qin Xu 5 , Hanhui Ye 6 , Wenyan Guo 1 , Jiao He 1 , Yahong Chen 6 , Ruixing Wang 1 , Zhijuan Wu 1 , Jing Yu 1
Affiliation  

Background: Effective antiretroviral therapy extends the survival of patients with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome, but these patients remain at higher risk for heart diseases compared with the general population. Previous studies have suggested that HIV-1 glycoprotein 120 (gp120) may be associated with heart disease. However, the underlying mechanisms by which HIV-1 gp120-mediated myocardial injury occurs remain unknown. Objective: The current study aimed to uncover the mechanism of C-C chemokine receptor 5 (CCR5) coreceptor (R5) HIV-1 gp120-induced myocardial injury. Methods: Morphology analysis, determination of the percentage of cell apoptosis, as well as lactate dehydrogenase (LDH) and creatine kinase (CK) assays were used to analyze whether R5 HIV-1 gp120 induced myocardial cell injury. We analyzed the phosphorylation of p38 mitogen-activated protein kinase (MAPK) with the CCR5 antagonist D-Ala-peptide T-amide (DAPTA) and NMDA receptor antagonist MK801, detected LDH and CK assays with p38 MAPK antagonist SB203580 (SB), and detected the percentage of cell apoptosis and death with DAPTA to investigate the mechanism of R5 HIV-1 gp120-induced myocardial cell injury. Results: R5 HIV-1 gp120 damaged myocardial cells and induced p38 MAPK phosphorylation. SB blocked R5 HIV-1 gp120-induced myocardial cell injury. DAPTA blocked R5 HIV-1 gp120-mediated p38 MAPK phosphorylation, while MK801 did not. DAPTA inhibited R5 HIV-1 gp120-induced myocardial cell injury. Conclusion: Our data indicate that R5 HIV-1 gp120 activated p38 MAPK to trigger myocardial cell injury by the CCR5 coreceptor.

中文翻译:

R5 HIV-1 gp120 激活 p38 MAPK 以通过 CCR5 辅助受体诱导大鼠心肌细胞损伤

背景:有效的抗逆转录病毒治疗延长了人类免疫缺陷病毒 (HIV)/获得性免疫缺陷综合征患者的生存期,但与普通人群相比,这些患者患心脏病的风险仍然较高。先前的研究表明,HIV-1 糖蛋白 120 (gp120) 可能与心脏病有关。然而,HIV-1 gp120 介导的心肌损伤发生的潜在机制仍然未知。目的:本研究旨在揭示CC趋化因子受体5(CCR5)辅助受体(R5)HIV-1 gp120诱导心肌损伤的机制。方法:通过形态学分析、细胞凋亡百分比的测定,以及乳酸脱氢酶(LDH)和肌酸激酶(CK)测定来分析R5 HIV-1 gp120是否诱导心肌细胞损伤。我们用 CCR5 拮抗剂 D-Ala-肽 T-酰胺 (DAPTA) 和 NMDA 受体拮抗剂 MK801 分析了 p38 丝裂原活化蛋白激酶 (MAPK) 的磷酸化,用 p38 MAPK 拮抗剂 SB203580 (SB) 检测了 LDH 和 CK 测定,以及用 DAPTA 检测细胞凋亡和死亡的百分比,以研究 R5 HIV-1 gp120 诱导心肌细胞损伤的机制。结果:R5 HIV-1 gp120 损伤心肌细胞并诱导 p38 MAPK 磷酸化。SB 阻断了 R5 HIV-1 gp120 诱导的心肌细胞损伤。DAPTA 阻断了 R5 HIV-1 gp120 介导的 p38 MAPK 磷酸化,而 MK801 则没有。DAPTA 抑制 R5 HIV-1 gp120 诱导的心肌细胞损伤。结论:我们的数据表明 R5 HIV-1 gp120 激活 p38 MAPK 以通过 CCR5 辅助受体触发心肌细胞损伤。
更新日期:2019-01-01
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