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L-肉碱和β-丙氨酸改善低氧诱导骨骼肌蛋白丢失的比较生化研究

A Comparative Biochemical Study Between L-Carnosine and β-Alanine in Amelioration of Hypobaric Hypoxia-Induced Skeletal Muscle Protein Loss.

机构信息

Pathophysiology and Disruptive Technologies, Defense Institute of Physiology and Allied Sciences (DIPAS), New Delhi, India.

出版信息

High Alt Med Biol. 2023 Dec;24(4):302-311. doi: 10.1089/ham.2023.0014. Epub 2023 Aug 28.

DOI:10.1089/ham.2023.0014
PMID:37643283
Abstract

Rathor, Richa, Sukanya Srivastava, and Geetha Suryakumar. A comparative biochemical study between L-carnosine and β-alanine in amelioration of hypobaric hypoxia-induced skeletal muscle protein loss. . 24:302-311, 2023. Carnosine (CAR; β-alanyl-L-histidine), a biologically active dipeptide is known for its unique pH-buffering capacity, metal chelating activity, and antioxidant and antiglycation property. β-Alanine (ALA) is a nonessential amino acid and used to enhance performance and cognitive functions. Hypobaric hypoxia (HH)-induced muscle protein loss is regulated by multifaceted signaling pathways. The present study investigated the beneficial effects of CAR and ALA against HH-associated muscle loss. Simulated HH exposure was performed in an animal decompression chamber. Gastric oral administration of CAR (50 mg·kg) and ALA (450 mg·kg) were given daily for 3 days and at the end of the treatment, hindlimb skeletal muscle tissue was excised for western blot and biochemical assays. Cosupplementation of CAR and ALA alone was able to ameliorate the hypoxia-induced inflammation, oxidative stress (FOXO), ER stress (GRP-78), and atrophic signaling (MuRF-1) in the skeletal muscles. Creatinine phospho kinase activity and apoptosis were also decreased in CAR- and ALA-supplemented rats. However, CAR showed enhanced protection in HH-induced muscle loss as CAR supplementation was able to enhance protein concentration, body weight, and decreased the protein oxidation and ALA administration was not able to restore the same. Hence, the present comprehensive study supports the fact that CAR (50 mg·kg) is more beneficial as compared with ALA (450 mg·kg) in ameliorating the hypoxia-induced skeletal muscle loss.

摘要

拉索尔、里奇亚、苏坎亚·斯里瓦斯塔瓦和吉塔·苏里亚库玛。L-肉碱和 β-丙氨酸在减轻低氧诱导的骨骼肌蛋白损失中的比较生化研究。. 24:302-311, 2023. 肉碱(CAR;β-丙氨酰-L-组氨酸)是一种具有独特 pH 缓冲能力、金属螯合活性、抗氧化和抗糖化特性的生物活性二肽。β-丙氨酸(ALA)是一种非必需氨基酸,用于提高性能和认知功能。低氧诱导的肌肉蛋白损失受多方面信号通路的调节。本研究探讨了 CAR 和 ALA 对 HH 相关肌肉损失的有益作用。 在动物减压舱中进行模拟低氧暴露。每天给予胃口服 CAR(50mg·kg)和 ALA(450mg·kg),连续 3 天,治疗结束时,切除后肢骨骼肌组织进行 Western blot 和生化分析。 CAR 和 ALA 的联合补充能够改善低氧诱导的炎症、氧化应激(FOXO)、内质网应激(GRP-78)和萎缩信号(MuRF-1)在骨骼肌中的作用。肌酸磷酸激酶活性和凋亡也在 CAR 和 ALA 补充的大鼠中降低。然而,CAR 表现出对 HH 诱导的肌肉损失的增强保护作用,因为 CAR 补充能够增加蛋白质浓度、体重,并降低蛋白质氧化,而 ALA 给药则不能恢复相同的效果。 因此,本综合研究支持这样一个事实,即与 ALA(450mg·kg)相比,CAR(50mg·kg)在改善低氧诱导的骨骼肌损失方面更有益。

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