Crotonaldehyde induces heat shock protein 72 expression that mediates anti-apoptotic effects in human endothelial cells

Dong Sun Ryu, Hana Yang, Seung Eun Lee, Cheung Seog Park, Young Ho Jin, Yong Seek Park

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13 Scopus citations


Crotonaldehyde is a highly reactive aldehyde and a common environmental pollutant. It occurs in cigarette smoke and automobile exhaust, and is also endogenously generated by lipid peroxidation. Reactive aldehydes, such as crotonaldehyde, are considered to be important mediators of cell damage. Since endothelial apoptosis is considered to be the first step in the pathogenesis of cardiovascular disease, there have been many efforts to protect endothelial cell from oxidative stress. Heat shock protein 72 (HSP72) is a representative stress-inducible HSP70 family protein, and its synthesis is increased in response to multiple stressors. In the present study, we investigated the effect of crotonaldehyde on the up-regulation of HSP72 in human umbilical vein endothelial cells (HUVECs). Crotonaldehyde treatment caused nuclear accumulation of the heat shock transcription factor 1 (HSF1), leading to the induction of HSP72. Inhibition of the c-Jun N-terminal kinases (JNK) signaling pathways, reduction of intracellular calcium level and blocking of reactive oxygen species (ROS) generation resulted in significant blockage of crotonaldehyde-mediated HSP72 induction. In addition, HSP72 silencing by siRNA or calcium chelating by BAPTA/AM resulted in an obvious increase in the rate of apoptosis in crotonaldehyde-stimulated HUVECs. In summary, our data demonstrated that crotonaldehyde-induced HSP72 expression in HUVECs is mediated by the JNK-HSF1 pathway, and involves calcium ions and ROS, which is an adaptive response to oxidative stress caused by crotonaldehyde.

Original languageEnglish (US)
Pages (from-to)116-123
Number of pages8
JournalToxicology Letters
Issue number2
StatePublished - Nov 25 2013

Bibliographical note

Funding Information:
This study was supported by a grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea ( A111834 ).


  • Apoptosis
  • Cardiovascular diseases
  • Crotonaldehyde
  • Endothelial cells
  • Heat shock protein 72
  • Heat shock proteins


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