Cited by 24Heat shock proteins researchGenetics, Aging, and Longevity in Model OrganismsRedox biology and oxidative stress

Hsp22 Overexpression Induces Myocardial Hypertrophy, Senescence and Reduced Life Span through Enhanced Oxidative Stress

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Morin, Didier, Long, Romain, Panel, Mathieu, Laure, Lydie, Taranu, Adela, Gueguen, Cindy, Pons, Sandrine, Leoni, Valerio +7 more·2019·Free Radical Biology and Medicine

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.

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Crossref · 10.1016/j.freeradbiomed.2019.04.035

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Authors
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.
Affiliations
  • Inserm (FR)
  • University of Milano-Bicocca (IT)
  • Fondazione IRCCS Istituto Neurologico Carlo Besta (IT)
  • Rutgers, The State University of New Jersey (US)
Corresponding author
Morin, Didier
Venue
Free Radical Biology and Medicine
Publisher
Elsevier BV
Published
2019-06
Volume
137
Pages
194-200
ISSN
0891-5849 (ISSN-L)
OpenAlex
W2943097203
Cited by
24
References
45
Citations by year
2026: 2 · 2025: 4 · 2024: 2 · 2023: 5 · 2022: 3 · 2021: 4 · 2020: 4
FWCI
0.91
Type
journal article
Language
en
Open access
Locations
  • Free Radical Biology and Medicine (acceptedVersion)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • BOA (University of Milano-Bicocca) (submittedVersion)
Funders
Ministère de la Recherche et de la Technologie
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heat shock proteins research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
Hsp22, small heat shock proteins, cardiac hypertrophy, cellular senescence, oxidative stress, reactive oxygen species, glutathione, tempol, Akt phosphorylation, telomerase activity, p16, p19, aging, transgenic mice
MeSH terms
Animals, Antioxidants, Cells, Cultured, Cyclic N-Oxides, Heat-Shock Proteins, Longevity, Male, Mice, Transgenic, Mitochondria, Myocardium, Phosphorylation, Spin Labels, Cellular Senescence, Hypertrophy, Left Ventricular, Reactive Oxygen Species, Oxidative Stress, Molecular Chaperones, Proto-Oncogene Proteins c-akt, Mice

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