Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress

Didier Morin, Romain Long, Mathieu Panel, Lydie Laure, Adela Taranu, Cindy Gueguen, Sandrine Pons, Valerio Leoni, Claudio Caccia, Stephen F. Vatner, Dorothy E. Vatner, Hongyu Qiu, Christophe Depre, Alain Berdeaux, Bijan Ghaleh

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

H11 kinase/Hsp22 (Hsp22) is a small heat shock protein, which, when overexpressed cardiac specifically in transgenic (TG) mice, induces stable left ventricular (LV) hypertrophy. Hsp22 also increases oxidative phosphorylation and mitochondrial reactive oxygen species (ROS) production, mechanisms mediating LV hypertrophy, senescence and reduced lifespan. Therefore, we investigated whether ROS production mediates LV hypertrophy, senescence and reduced life span in Hsp22 TG mice. Survival curves revealed that TG mice had a 48% reduction in their mean life span compared to wild type (WT) mice. This was associated with a significant increase in senescence markers, such as p16, p19 mRNA levels as well as the percentage of β-galactosidase positive cells and telomerase activity. Oxidized (GSSG)/reduced (GSH) glutathione ratio, an indicator of oxidative stress, and ROS production from 3 major cellular sources was measured in cardiac tissue. Hearts from TG mice exhibited a decrease in GSH/GSSG ratio together with increased ROS production from all sources. To study the role of ROS, mice were treated with the antioxidant Tempol from weaning to their sacrifice. Chronic Tempol treatment abolished oxidative stress and overproduction of ROS, and reduced myocardial hypertrophy and Akt phosphorylation in TG mice. Tempol also significantly extended life span and prevented aging markers in TG mice. Taken together these results show that overexpression of Hsp22 increases oxidative stress responsible for the induction of hypertrophy and senescence and ultimately reduction in life span.

Original languageEnglish (US)
Pages (from-to)194-200
Number of pages7
JournalFree Radical Biology and Medicine
Volume137
DOIs
StatePublished - Jun 2019

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Keywords

  • Hsp22 overexpression
  • Life span
  • Myocardial hypertrophy
  • Oxidative stress
  • Senescence

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    Morin, D., Long, R., Panel, M., Laure, L., Taranu, A., Gueguen, C., Pons, S., Leoni, V., Caccia, C., Vatner, S. F., Vatner, D. E., Qiu, H., Depre, C., Berdeaux, A., & Ghaleh, B. (2019). Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress. Free Radical Biology and Medicine, 137, 194-200. https://doi.org/10.1016/j.freeradbiomed.2019.04.035