Dominant negative 14-3-3 promotes cardiomyocyte apoptosis in early stage of type I diabetes mellitus through activation of JNK.

14-3-3 family members are dimeric, phosphoserine binding proteins that regulate signal transduction, apoptotic, and checkpoint control pathways. Recently, cardiomyocyte apoptosis has been characterized in type I diabetes mellitus. In order to study the molecular mechanism underlying diabetes-induced cardiomyocyte apoptosis, we examined the role of 14-3-3 protein and MAPK pathways in transgenic mice with cardiac specific expression of dominant negative 14-3-3eta (DN-14-3-3). p38 MAPK was highly activated 1, 28, and 56 days after diabetes induction by streptozotocin, whereas peak JNK activation was found on day 3 and decreased afterwards. In contrast, ERK1/2 were not activated in diabetic myocardium. Cardiomyocyte apoptosis was peaked on day 3 and decreased on 7, 28, and 56 days. p38 MAPK and JNK activation as well as cardiomyocyte apoptosis were greatly increased in DN-14-3-3 mice relative to non-transgenic mice. Moreover, we found a significant correlation between JNK activation and apoptosis in diabetic myocardium. These results indicate for the first time that 14-3-3 protein plays a critical anti-apoptotic role in diabetic myocardium by inhibiting the JNK pathway.

• Publication year

  2004

• Venue

  Biochemical and Biophysical Research Communications - BBRC

• Publication date

  2004-07-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/J.BBRC.2004.06.023PMID 15240115
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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