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 Vatner, Dorothy Vatner, Hongyu Qiu, Christophe Depre, Alain Berdeaux, Bijan Ghaleh

Research output: Contribution to journalArticle

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 1 2019

Fingerprint

Oxidative stress
Hypertrophy
Transgenic Mice
Reactive Oxygen Species
Oxidative Stress
Left Ventricular Hypertrophy
Glutathione Disulfide
Galactosidases
Small Heat-Shock Proteins
Phosphorylation
Telomerase
Oxidative Phosphorylation
Weaning
Glutathione
Phosphotransferases
Antioxidants
Aging of materials
Cells
Tissue
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Physiology (medical)
  • Biochemistry

Keywords

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

Cite this

Morin, Didier ; Long, Romain ; Panel, Mathieu ; Laure, Lydie ; Taranu, Adela ; Gueguen, Cindy ; Pons, Sandrine ; Leoni, Valerio ; Caccia, Claudio ; Vatner, Stephen ; Vatner, Dorothy ; Qiu, Hongyu ; Depre, Christophe ; Berdeaux, Alain ; Ghaleh, Bijan. / Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress. In: Free Radical Biology and Medicine. 2019 ; Vol. 137. pp. 194-200.
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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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Morin, D, Long, R, Panel, M, Laure, L, Taranu, A, Gueguen, C, Pons, S, Leoni, V, Caccia, C, Vatner, S, Vatner, D, 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, vol. 137, pp. 194-200. https://doi.org/10.1016/j.freeradbiomed.2019.04.035

Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress. / Morin, Didier; Long, Romain; Panel, Mathieu; Laure, Lydie; Taranu, Adela; Gueguen, Cindy; Pons, Sandrine; Leoni, Valerio; Caccia, Claudio; Vatner, Stephen; Vatner, Dorothy; Qiu, Hongyu; Depre, Christophe; Berdeaux, Alain; Ghaleh, Bijan.

In: Free Radical Biology and Medicine, Vol. 137, 01.06.2019, p. 194-200.

Research output: Contribution to journalArticle

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T1 - Hsp22 overexpression induces myocardial hypertrophy, senescence and reduced life span through enhanced oxidative stress

AU - Morin, Didier

AU - Long, Romain

AU - Panel, Mathieu

AU - Laure, Lydie

AU - Taranu, Adela

AU - Gueguen, Cindy

AU - Pons, Sandrine

AU - Leoni, Valerio

AU - Caccia, Claudio

AU - Vatner, Stephen

AU - Vatner, Dorothy

AU - Qiu, Hongyu

AU - Depre, Christophe

AU - Berdeaux, Alain

AU - Ghaleh, Bijan

PY - 2019/6/1

Y1 - 2019/6/1

N2 - 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.

AB - 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.

KW - Hsp22 overexpression

KW - Life span

KW - Myocardial hypertrophy

KW - Oxidative stress

KW - Senescence

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