Ghanemi Abdelaziz, Yoshioka Mayumi, St-Amand Jonny
Functional Genomics Laboratory, Endocrinology and Nephrology Axis, CHU de Québec-Université Laval Research Center, Quebec, QC G1V 4G2, Canada.
Faculty of Pharmacy, Laval University, Quebec, QC G1V 0A6, Canada.
Biology (Basel). 2025 Apr 10;14(4):398. doi: 10.3390/biology14040398.
Secreted protein acidic and rich in cysteine (SPARC) is a protein widely expressed in various tissues. The metabolic and functional exploration of SPARC indicated it as a mediator of the exercise-induced effects. Furthermore, SPARC overexpression mimics exercise effects (including anti-aging phenotype), whereas its knockout both reduces the exercise-induced phenotype and increases aging. Each of these previous studies has been carried out for weeks and, therefore, indicates chronic effects of SPARC. To complete the puzzle, there is a need to explore the acute effects of SPARC. Thus, this study reports results of selected molecular and metabolic explorations of mice following a single injection of SPARC. Following both a validation of the Western blot as a detection method of SPARC in the serum and the optimization of the post-injection sacrifice time, mice (male and female) were injected with either SPARC or saline and sacrificed after 4 h. Body weight, selected tissues weights, and glycemia were measured. Muscle (tibialis anterior)-that was also harvested after the sacrifice and frozen-was used to measure the expression of selected proteins related to metabolism, protein hemostasis, and muscle development. Briefly, the results indicate a protein expression pattern towards improved glucose metabolism, oxidative phosphorylation, mitochondrial biogenesis, extracellular matrix remodeling, myogenesis, and protein synthesis. On the other hand, the expression of other proteins is towards decreased muscle protein degradation. There were no significant effects of SPARC injection on glycemia. These findings represent an important step towards developing a pharmacology based on injecting SPARC to achieve therapeutic effects that basically mimic exercise benefits, including anti-aging, metabolic enhancement, and muscle development. This is of particular importance for individuals who are unable to perform the required physical activity due to physical disabilities, aging, or hospitalization.
富含半胱氨酸的酸性分泌蛋白（SPARC）是一种在各种组织中广泛表达的蛋白质。对SPARC的代谢和功能研究表明，它是运动诱导效应的介质。此外，SPARC的过表达模拟了运动效应（包括抗衰老表型），而其基因敲除既降低了运动诱导的表型，又加速了衰老。之前的每项研究都持续了数周，因此表明了SPARC的慢性影响。为了完善这一难题，有必要探索SPARC的急性影响。因此，本研究报告了单次注射SPARC后小鼠的选定分子和代谢研究结果。在验证了蛋白质印迹法作为血清中SPARC的检测方法并优化了注射后处死时间后，给雄性和雌性小鼠注射SPARC或生理盐水，并在4小时后处死。测量体重、选定组织的重量和血糖。处死小鼠后采集并冷冻的胫前肌用于测量与代谢、蛋白质稳态和肌肉发育相关的选定蛋白质的表达。简而言之，结果表明蛋白质表达模式朝着改善葡萄糖代谢、氧化磷酸化、线粒体生物发生、细胞外基质重塑、肌生成和蛋白质合成的方向发展。另一方面，其他蛋白质的表达则朝着减少肌肉蛋白质降解的方向发展。注射SPARC对血糖没有显著影响。这些发现代表了开发一种基于注射SPARC以实现基本模拟运动益处（包括抗衰老、代谢增强和肌肉发育）的治疗效果的药理学的重要一步。这对于因身体残疾、衰老或住院而无法进行所需体育活动的个体尤为重要。
