Peer-reviewedCC BYJournal of cellular and molecular medicine30 Oct 2026

DBT Modulates Copper-Dependent Cuproptosis-Related Injury in Experimental Alcoholic Cardiomyopathy.

Zhihao Pan¹
Liuming Gao²
Yi Ling¹
Xianfeng Cen³

¹Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
²Medical Research Institute of Wuhan University, Wuhan, Hubei, China.
³Department of Cardiovascular Surgery, Lihuili Hospital Affiliated to Ningbo University, Ningbo, Zhejiang, China.

Abstract

Alcoholic cardiomyopathy (ACM) is a severe cardiovascular complication of chronic alcohol consumption, but its underlying mechanisms remain incompletely understood. Cuproptosis is a recently identified copper-dependent form of regulated cell death; however, its role in ACM remains unclear. In this study, male C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli liquid diet to establish an ACM model, and RNA sequencing combined with bioinformatics analysis was performed to identify cuproptosis-related genes. Among the candidate genes, dihydrolipoamide branched-chain transacylase E2 (DBT) showed a consistent trend of downregulation across both independent RNA-seq cohorts, and was further validated by qRT-PCR and Western blotting. ACM mice exhibited increased serum and cardiomyocyte copper content, altered cuproptosis-related markers and impaired cardiac function. In AC16 cells, DBT knockdown induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, which were markedly alleviated by the copper chelator tetrathiomolybdate. Conversely, DBT overexpression attenuated EtOH-induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, with effects similar to those of tetrathiomolybdate. These findings suggest that DBT regulates ACM-related cardiomyocyte injury through cuproptosis-associated processes at the cellular level and may represent a potential therapeutic target for alcohol-induced myocardial injury.

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Cite

BibTeX RIS

BibTeX

@article{pan2026modulates,
  title = {{DBT Modulates Copper-Dependent Cuproptosis-Related Injury in Experimental Alcoholic Cardiomyopathy.}},
  author = {Zhihao Pan and Liuming Gao and Yi Ling and Xianfeng Cen},
  journal = {Journal of cellular and molecular medicine},
  year = {2026},
  month = oct,
  doi = {10.1111/jcmm.71421},
  url = {https://europepmc.org/article/MED/42963828},
  note = {CC BY},
}

RIS

TY  - JOUR
TI  - DBT Modulates Copper-Dependent Cuproptosis-Related Injury in Experimental Alcoholic Cardiomyopathy.
AU  - Zhihao Pan
AU  - Liuming Gao
AU  - Yi Ling
AU  - Xianfeng Cen
PY  - 2026
DA  - 2026/10/30
JO  - Journal of cellular and molecular medicine
DO  - 10.1111/jcmm.71421
UR  - https://europepmc.org/article/MED/42963828
AB  - Alcoholic cardiomyopathy (ACM) is a severe cardiovascular complication of chronic alcohol consumption, but its underlying mechanisms remain incompletely understood. Cuproptosis is a recently identified copper-dependent form of regulated cell death; however, its role in ACM remains unclear. In this study, male C57BL/6 mice were fed an ethanol-containing Lieber-DeCarli liquid diet to establish an ACM model, and RNA sequencing combined with bioinformatics analysis was performed to identify cuproptosis-related genes. Among the candidate genes, dihydrolipoamide branched-chain transacylase E2 (DBT) showed a consistent trend of downregulation across both independent RNA-seq cohorts, and was further validated by qRT-PCR and Western blotting. ACM mice exhibited increased serum and cardiomyocyte copper content, altered cuproptosis-related markers and impaired cardiac function. In AC16 cells, DBT knockdown induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, which were markedly alleviated by the copper chelator tetrathiomolybdate. Conversely, DBT overexpression attenuated EtOH-induced copper overload, cuproptosis-related molecular alterations and mitochondrial dysfunction, with effects similar to those of tetrathiomolybdate. These findings suggest that DBT regulates ACM-related cardiomyocyte injury through cuproptosis-associated processes at the cellular level and may represent a potential therapeutic target for alcohol-induced myocardial injury.
SN  - 1582-1838
SN  - 1582-4934
ER  -