Glutamine Suppresses Senescence and Promotes Autophagy Through Glycolysis Inhibition-mediated AMPKα Lactylation in Intervertebral Disc Degeneration

Overview

Journal Commun Biol

Specialty Biology

Date 2024 Mar 15

PMID 38486093

Authors

Yangyang Zhang

Zhengqi Huang

Weitao Han

Jiajun Wu

Shuangxing Li

Tianyu Qin

Chao Zhang

Ming Shi

Shun Han

Bo Gao

Song Jin

Yin Xiao

Kang Xu

Wei Ye

Affiliations

Soon will be listed here.

Abstract

Regulating metabolic disorders has become a promising focus in treating intervertebral disc degeneration (IDD). A few drugs regulating metabolism, such as atorvastatin, metformin, and melatonin, show positive effects in treating IDD. Glutamine participates in multiple metabolic processes, including glutaminolysis and glycolysis; however, its impact on IDD is unclear. The current study reveals that glutamine levels are decreased in severely degenerated human nucleus pulposus (NP) tissues and aging Sprague-Dawley (SD) rat nucleus pulposus tissues, while lactate accumulation and lactylation are increased. Supplementary glutamine suppresses glycolysis and reduces lactate production, which downregulates adenosine-5'-monophosphate-activated protein kinase α (AMPKα) lactylation and upregulates AMPKα phosphorylation. Moreover, glutamine treatment reduces NP cell senescence and enhances autophagy and matrix synthesis via inhibition of glycolysis and AMPK lactylation, and glycolysis inhibition suppresses lactylation. Our results indicate that glutamine could prevent IDD by glycolysis inhibition-decreased AMPKα lactylation, which promotes autophagy and suppresses NP cell senescence.

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