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Pyruvate kinase M2 modification by a lipid peroxidation byproduct acrolein contributes to kidney fibrosis

ABSTRACT: This study used a proteomic approach with an anti-Acr-PC antibody followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis to identify several acrolein-modified protein targets. Among these protein targets, pyruvate kinase M2 (PKM2) was found to be modified by acrolein at Cys358, leading to the inactivation of PKM2 contributing to the pathogenesis of renal fibrosis through HIF1 accumulation, aberrant glycolysis, and upregulation of EMT in HFD-STZ-induced DN mice. Finally, PKM2 activity and renal fibrosis in DN mice can be reduced by acrolein scavengers such as hydralazine and carnosine. These results imply that acrolein-modified PKM2 contributes to renal fibrosis in the pathogenesis of DN.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Kidney

DISEASE(S): Type 2 Diabetes Mellitus

SUBMITTER: Hsiang-Tsui Wang

LAB HEAD: Hsiang-Tsui Wang

PROVIDER: PXD040335 | Pride | 2023-05-10

REPOSITORIES: Pride

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Pyruvate kinase M2 modification by a lipid peroxidation byproduct acrolein contributes to kidney fibrosis.

Kuo Chin-Wei CW Chen Dong-Hao DH Tsai Ming-Tsun MT Lin Chih-Ching CC Cheng Hsiao-Wei HW Tsay Yeou-Guang YG Wang Hsiang-Tsui HT

Frontiers in medicine 20230315

Renal fibrosis is a hallmark of diabetic nephropathy (DN) and is characterized by an epithelial-to-mesenchymal transition (EMT) program and aberrant glycolysis. The underlying mechanisms of renal fibrosis are still poorly understood, and existing treatments are only marginally effective. Therefore, it is crucial to comprehend the pathophysiological mechanisms behind the development of renal fibrosis and to generate novel therapeutic approaches. Acrolein, an α-,β-unsaturated aldehyde, is endogeno ...[more]

PMID: 37007793

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