MUSCLE AMINO ACID METABOLISM IN AIDS CACHEXIA

艾滋病恶病质中的肌肉氨基酸代谢

• 批准号: 6486813
• 负责人: KE YARASHESKI
• 金额: $ 15.75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6486813
• 关键词: biological products; biomedical equipment development; biomedical resource; immunology; inflammation; lipids; nucleic acids; proteins; spectrometry; technology /technique

Muscle protein wasting occurs in HIV-infected individuals and is often the initial indication of AIDS. The alterations in muscle protein metabolism that explain AIDS-wasting are unknown. Seven subjects with AIDS-wasting (CD4<200/mm3, HIV mRNA= 7.1x105 copies/ml) chronic stable opportunistic infections (OI) and >10% weight loss, 10 HIV-infected men and 1 woman (CD4>200/mm3, HIV mRNA= 3.3x103 copies/ml) without wasting or OI (asymptomatic), and 6 HIV-negative lean men (control) were studied. Constant intravenous infusions of 1-[13C]-leucine and 2-[15N]-glutamine were used to assess plasma leucine and glutamine rate of appearance (Ra), whole-body leucine oxidation rate, and 13C-leucine incorporation rate into whole-body and mixed muscle protein. Fasting whole-body proteolysis and synthesis rates were increased (P<0.05) above control in the asymptomatic HIV-infected subjects, and further increased (P<0.05) in AIDS-wasting. Fasting mixed muscle protein synthesis rate was increased in the asymptomatic subjects (P<0.05), but similar in AIDS-wasting and control subjects. Plasma glutamine Ra was increased (P<0.001) in AIDS-wasting subjects, but similar in control and asymptomatic subjects. These findings suggest that AIDS-wasting results from; (a) a preferential reduction in muscle protein, (b) a failure to sustain an elevated rate of mixed muscle protein synthesis while whole-body protein turnover is increased, and (c) a significant increase in glutamine release into the circulation, probably from muscle proteolysis. The reason for the increased glutamine Ra in AIDS-wasting is unknown, but several interesting possibilities exist.

HIV 感染者会出现肌肉蛋白消耗，并且 通常是艾滋病的最初迹象。 肌肉的变化 解释艾滋病消耗的蛋白质代谢尚不清楚。 七 艾滋病消瘦患者（CD4<200/mm3，HIV mRNA= 7.1x105 拷贝/ml） 慢性稳定机会性感染 (OI) 和体重减轻 >10%，10 HIV 感染男性和 1 名女性（CD4>200/mm3，HIV mRNA= 3.3x103 拷贝数/ml），无浪费或 OI（无症状），以及 6 个 HIV 阴性 研究对象是瘦男性（对照组）。 持续静脉输注 1-[13C]-亮氨酸和2-[15N]-谷氨酰胺用于评估血浆 亮氨酸和谷氨酰胺出现率 (Ra)，全身亮氨酸 氧化速率和 13C-亮氨酸掺入全身和 混合肌肉蛋白。 空腹全身蛋白水解和合成 无症状患者的发病率高于对照（P<0.05） HIV感染者的艾滋病消瘦进一步增加（P<0.05）。 空腹混合肌蛋白合成率为 增加 在无症状受试者中（P<0.05），但在艾滋病消耗者中相似 和控制对象。 血浆谷氨酰胺 Ra 升高 (P<0.001) 患有艾滋病的受试者，但在对照和无症状方面相似 科目。 这些发现表明艾滋病消瘦的原因是： （一个） 肌肉蛋白优先减少，(b) 无法维持 混合肌肉蛋白质合成率升高，同时全身 蛋白质周转率增加，并且 (c) 显着增加 谷氨酰胺释放到循环中，可能是从肌肉中 蛋白水解。 谷氨酰胺Ra升高的原因 艾滋病导致的消耗尚不清楚，但存在一些有趣的可能性。