REDUCING PLASMA HIV RNA IMPROVES MUSCLE AMINO ACID METABOLISM

减少血浆 HIV RNA 改善肌肉氨基酸代谢

• 批准号: 7355251
• 负责人: KEVIN E YARASHESKI
• 金额: $ 1.39万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2007-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355251
• 关键词: REDUCING; PLASMA; HIV; RNA; IMPROVES

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577-E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln). We hypothesized that high plasma HIV RNA caused dysregulation of muscle amino acid metabolism. We determined whether a reduction in HIV RNA ( 1 log) increased muscle protein synthesis rate and reduced Ra Gln and muscle proteasome activity in 10 men and 1 woman (22-57 yr, 60-108 kg, 17-33 kg muscle) with advanced HIV (CD4 = 0-311 cells/¿l; HIV RNA = 10-375 x 103 copies/ml). We utilized stable isotope tracer methodologies ([13C]Leu and [15N]Gln) to measure the fractional rate of mixed muscle protein synthesis and plasma Ra Gln in these subjects before and 4 mo after initiating their first or a salvage antiretroviral therapy regimen. After treatment, median CD4 increased (98 vs. 139 cells/¿l, P = 0.009) and median HIV RNA was reduced (155,828 vs. 100 copies/ml, P = 0.003). Mixed muscle protein synthesis rate increased (0.062 ¿ 0.005 vs. 0.078 ¿ 0.006%/h, P = 0.01), Ra Gln decreased (387 ¿ 33 vs. 323 ¿ 15 ¿mol?kg fat-free mass -1 h -1, P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% (P = 0.03). Muscle mass was only modestly increased (1 kg, P = not significant). We estimated that, for each 10,000 copies/ml reduction in HIV RNA, 3 g of additional muscle protein are synthesized per day. These findings suggest that reducing HIV RNA increases muscle protein synthesis and reduces muscle proteolysis, but muscle protein synthesis relative to whole body protein synthesis rate is not restored to normal, so muscle mass is not substantially increased.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是针对该中心的，这不是调查人员的机构。 We reported (Yarasheski KE, Zachwieja JJ, Gischler J, Crowley J, Horgan MM, and Powderly WG. Am J Physiol Endocrinol Metab 275: E577-E583, 1998) that AIDS muscle wasting was associated with an inappropriately low rate of muscle protein synthesis and an elevated glutamine rate of appearance (Ra Gln).我们假设高血浆HIV RNA引起肌肉氨基酸代谢失调。我们确定HIV RNA（1 log）的降低是否增加了肌肉蛋白的合成速率，并降低了10名男性和1名女性（22-57年，60-108 kg，17-33 kg肌肉）的RA GLN和肌肉蛋白酶体的活性，其肌肉蛋白的合成速率增加了肌肉蛋白的合成率（CD4 = 0-311 = 0-311 cells/�lNA= 0-311 Cell/¿我们利用稳定的同位素示踪剂方法（[13C] LEU和[15n] GLN）在这些受试者中测量混合肌肉蛋白合成的分数速率和在启动其首次或萨尔维奇抗逆转录病毒治疗方案后4 mo中的质量。治疗后，中位CD4增加（98 vs.139个细胞/€，p = 0.009），并降低了HIV RNA的中位数（155,828 vs. 100拷贝/ml，p = 0.003）。 Mixed muscle protein synthesis rate increased (0.062 ¿ 0.005 vs. 0.078 ¿ 0.006%/h, P = 0.01), Ra Gln decreased (387 ¿ 33 vs. 323 ¿ 15 mol?kg fat-free mass -1 h -1, P = 0.04), and muscle proteasome chymotrypsin-like catalytic activity was reduced 14% (P = 0.03).肌肉质量仅适度增加（1 kg，p =不显着）。我们估计，对于HIV RNA的每10,000份/ml均降低，每天合成3 g额外的肌肉蛋白。这些发现表明，减少HIV RNA会增加肌肉蛋白的合成并减少肌肉蛋白解，但是相对于整个身体蛋白质合成率，肌肉蛋白的合成并未恢复到正常状态，因此肌肉质量并未大大增加。