Affiliation:
1. Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, China
2. The Scientific Research Center of Dongguan, Guangdong Medical University, Dongguan, China
3. Institute of Biochemistry & Molecular Biology, Guangdong Medical University, Zhanjiang, China
Abstract
The cytosolic isozyme of phosphoenolpyruvate carboxykinase (PCK1) was the first rate-limiting enzyme in the gluconeogenesis pathway, which exerted a critical role in maintaining the blood glucose levels.PCK1has been established to be involved in various physiological and pathological processes, including glucose metabolism, lipid metabolism, diabetes, and tumorigenesis. Nonetheless, the association ofPCK1with aging process and the detailed underlying mechanisms ofPCK1on aging are still far to be elucidated. Hence, we herein constructed thePCK1-deficient (pck1Δ) andPCK1overexpression (PCK1 OE)Saccharomyces cerevisiae. The results unveiled thatPCK1deficiency significantly shortened the replicative lifespan (RLS) in theS. cerevisiae, while overexpression ofPCK1prolonged the RLS. Additionally, we noted that the ROS level was significantly enhanced inPCK1-deficient strain and decreased inPCK1 OEstrain. Then, a high throughput analysis by deep sequencing was performed in thepck1Δ and wild-type strains, in an attempt to shed light on the effect ofPCK1on the lifespan of aging process. The data showed that the most downregulated mRNAs were enriched in the regulatory pathways of glucose metabolism. Fascinatingly, among the differentially expressed mRNAs,PFK1was one of the most upregulated genes, which was involved in the glycolysis process and ROS generation. Thus, we further constructed thepfk1Δpck1Δ strain by deletion ofPFK1in thePCK1-deficient strain. The results unraveled thatpfk1Δpck1Δ strain significantly suppressed the ROS level and restored the RLS ofpck1Δ strain. Taken together, our data suggested thatPCK1deficiency enhanced the ROS level and shortened the RLS ofS. cerevisiaeviaPFK1.
Funder
National Natural Science Foundation of China
Subject
General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine
Cited by
4 articles.
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