Systematic analysis of lysine lactylation in nucleus pulposus cells

Lei Sheng; Haoran Xu; Yuexing Wang; Jinhao Ni; Taiyang Xiang; Huanhuan Xu; Xiaozhong Zhou; Kang Wei; Jun Dai

iScience (Nov 2024)

Systematic analysis of lysine lactylation in nucleus pulposus cells

Lei Sheng,
Haoran Xu,
Yuexing Wang,
Jinhao Ni,
Taiyang Xiang,
Huanhuan Xu,
Xiaozhong Zhou,
Kang Wei,
Jun Dai

Affiliations

Lei Sheng: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Haoran Xu: Department of Joint Surgery, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong 510000, China
Yuexing Wang: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Jinhao Ni: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Taiyang Xiang: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Huanhuan Xu: Department of Obstetrics and Gynecology, Wuhan Children’s Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430000, China
Xiaozhong Zhou: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China
Kang Wei: Department of Plastic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, Hubei 430071, China; Corresponding author
Jun Dai: Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, China; Corresponding author

Journal volume & issue: Vol. 27, no. 11
p. 111157

Abstract

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Summary: Nucleus pulposus (NP) resides in hypoxic microenvironment and NP cells (NPCs), primarily reply on glycolysis and producing high levels of lactate. Intracellular lactate drives lysine lactylation (Kla) as a newly epigenetic modification. However, the impact of Kla on NPCs remains unknown. Here, single-cell RNA sequencing (scRNA-seq) data suggested an altered balance between glycolysis and aerobic oxidation in intervertebral disc degeneration (IDD). Liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis displayed 3510 lactylation sites on 1052 non-histone proteins of NPCs isolated from rat cultured in normoxia and hypoxia. Moreover, there are 18 proteins with 129 Kla sites and 117 Kla sites in 27 proteins exclusively detected in normoxia and hypoxia group, respectively. Bioinformatics analysis displayed that these lactylated proteins are tightly related to ribosome, spliceosome and the VEGFA-VEGFA2 signaling pathway. Together, our study reveals that Kla may play an important role in regulating cellular metabolism of NPCs.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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