Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, Institute of Aging Research, Guangdong Medical University, Dongguan, China.
The Scientific Research Center of Dongguan, Guangdong Medical University, Dongguan, China.
Biomed Res Int. 2020 Feb 12;2020:3858465. doi: 10.1155/2020/3858465. eCollection 2020.
The cytosolic isozyme of phosphoenolpyruvate carboxykinase () was the first rate-limiting enzyme in the gluconeogenesis pathway, which exerted a critical role in maintaining the blood glucose levels. has been established to be involved in various physiological and pathological processes, including glucose metabolism, lipid metabolism, diabetes, and tumorigenesis. Nonetheless, the association of with aging process and the detailed underlying mechanisms of on aging are still far to be elucidated. Hence, we herein constructed the -deficient (Δ) and overexpression () . The results unveiled that deficiency significantly shortened the replicative lifespan (RLS) in the , while overexpression of prolonged the RLS. Additionally, we noted that the ROS level was significantly enhanced in -deficient strain and decreased in strain. Then, a high throughput analysis by deep sequencing was performed in the Δ and wild-type strains, in an attempt to shed light on the effect of on 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, was one of the most upregulated genes, which was involved in the glycolysis process and ROS generation. Thus, we further constructed the ΔΔ strain by deletion of in the -deficient strain. The results unraveled that ΔΔ strain significantly suppressed the ROS level and restored the RLS of Δ strain. Taken together, our data suggested that deficiency enhanced the ROS level and shortened the RLS of via .
细胞质同工酶磷酸烯醇式丙酮酸羧激酶（）是糖异生途径中的第一个限速酶，对维持血糖水平起着关键作用。已经确定参与了各种生理和病理过程，包括葡萄糖代谢、脂代谢、糖尿病和肿瘤发生。然而，与衰老过程的关联以及对衰老的详细潜在机制仍远未阐明。因此，我们构建了磷酸烯醇式丙酮酸羧激酶缺陷型（Δ）和过表达（）。结果表明，缺陷型显著缩短了衰老过程中的复制寿命（RLS），而过表达则延长了 RLS。此外，我们注意到缺陷型菌株中的 ROS 水平显著增强，而菌株中的 ROS 水平降低。然后，在Δ和野生型菌株中进行了高通量深度测序分析，试图阐明对衰老过程中寿命的影响。数据显示，下调最明显的 mRNA 富集在葡萄糖代谢的调控途径中。有趣的是，在差异表达的 mRNA 中，是上调最明显的基因之一，它参与糖酵解过程和 ROS 的产生。因此，我们通过在缺陷型菌株中缺失进一步构建了ΔΔ菌株。结果表明，ΔΔ菌株显著抑制了 ROS 水平并恢复了Δ菌株的 RLS。总之，我们的数据表明，缺陷型通过增加 ROS 水平和缩短 RLS 来增强衰老过程中的 ROS 水平。
