CHOP deficiency prevents methylglyoxal-induced myocyte apoptosis and cardiac dysfunction

Dae Hwan Nam, Jung Hwa Han, Tae Jin Lee, Tetsuro Shishido, Jae Hyang Lim, Geun Young Kim, Chang Hoon Woo

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48 Scopus citations


Epidemiological studies indicate that methylglyoxal (MGO) plasma levels are closely linked to diabetes and the exacerbation of diabetic cardiovascular complications. Recently, it was established that endoplasmic reticulum (ER) stress importantly contributes to the pathogenesis of diabetes and its cardiovascular complications. The objective of this study was to explore the mechanism by which diabetes instigates cardiomyocyte apoptosis and cardiac dysfunction via MGO-mediated myocyte apoptosis. Intriguingly, the MGO activated unfolded protein response pathway accompanying apoptotic events, such as cleavages of PARP-1 and caspase-3. In addition, Western blot analysis revealed that MGO-induced myocyte apoptosis was inhibited by depletion of CHOP with siRNA against Ddit3, the gene name for rat CHOP. To investigate the physiologic roles of CHOP in vivo, glucose tolerance and cardiac dysfunction were assessed in CHOP-deficient mice. No significant difference was observed between CHOP KO and littermate naïve controls in terms of the MGO-induced impairment of glucose tolerance. In contrast, myocyte apoptosis, inflammation, and cardiac dysfunction were significantly diminished in CHOP KO compared with littermate naïve controls. These results showed that CHOP is the key signal for myocyte apoptosis and cardiac dysfunction induced by MGO. These findings suggest a therapeutic potential of CHOP inhibition in the management of diabetic cardiovascular complications including diabetic cardiomyopathy.

Original languageEnglish
Pages (from-to)168-177
Number of pages10
JournalJournal of Molecular and Cellular Cardiology
StatePublished - 1 Aug 2015

Bibliographical note

Funding Information:
This study was supported by a grant of the National Research Foundation of Korea ( NRF-2013R1A1A1011264 ) and the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( A111520 ).

Publisher Copyright:
© 2015 Elsevier Ltd.


  • CHOP
  • Cardiac dysfunction
  • Diabetes
  • ER stress
  • Methylglyoxal


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