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Burns Trauma. 2019 Mar 11;7:8. doi: 10.1186/s41038-019-0146-3. eCollection 2019.

Cardiac proteomics reveals the potential mechanism of microtubule associated protein 4 phosphorylation-induced mitochondrial dysfunction.

Author information

1
1Institute of Burn Research, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038 China.
2
2Endocrinology Department, State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Gaotanyan Street, Shapingba District, Chongqing, 400038 China.
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Contributed equally

Abstract

Background:

Our previous work suggested that microtubule associated protein 4 (MAP4) phosphorylation led to mitochondrial dysfunction in MAP4 phosphorylation mutant mice with cardiomyopathy, but the detailed mechanism was still unknown. Thus, the aim of this study was to investigate the potential mechanism involved in mitochondrial dysfunction responsible for cardiomyopathy.

Methods:

The present study was conducted to explore the potential mechanism underlying the mitochondrial dysfunction driven by MAP4 phosphorylation. Strain of mouse that mimicked constant MAP4 phosphorylation (S737 and S760) was generated. The isobaric tag for relative and absolute quantitation (iTRAQ) analysis was applied to the heart tissue. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) were all analyzed on the basis of differential expressed proteins (DEPs).

Results:

Among the 72 cardiac DEPs detected between the two genotypes of mice, 12 were upregulated and 60 were downregulated. GO analysis showed the biological process, molecular function, and cellular component of DEPs, and KEGG enrichment analysis linked DEPs to 96 different biochemical pathways. In addition, the PPI network was also extended on the basis of DEPs as the seed proteins. Three proteins, including mitochondrial ubiquitin ligase activator of NF-κB 1, reduced form of nicotinamide adenine dinucleotide (NADH)-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial and growth arrest, and DNA-damage-inducible proteins-interacting protein 1, which play an important role in the regulation of mitochondrial function, may correlate with MAP4 phosphorylation-induced mitochondrial dysfunction. Western blot was used to validate the expression of the three proteins, which was consistent with iTRAQ experiments.

Conclusions:

These findings revealed that the DEPs caused by MAP4 phosphorylation in heart tissue using iTRAQ technique and may provide clues to uncover the potential mechanism of MAP4 phosphorylation-induced mitochondrial dysfunction.

KEYWORDS:

Isobaric tag for relative and absolute quantitation; Microtubule associated protein 4; Mitochondria

Conflict of interest statement

Animal experiments were performed in accordance with United Kingdom Home Office and European Union guidelines and were approved by the Animal Care Centre of the Army Medical University.Not applicable.The authors declare that they have no competing interests.

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