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 language | English (US) |
|---|---|
| Pages (from-to) | 194-200 |
| Number of pages | 7 |
| Journal | Free Radical Biology and Medicine |
| Volume | 137 |
| DOIs | |
| State | Published - Jun 1 2019 |
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All Science Journal Classification (ASJC) codes
- Biochemistry
- Physiology (medical)
Keywords
- Hsp22 overexpression
- Life span
- Myocardial hypertrophy
- Oxidative stress
- Senescence
Cite this
}
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 journal › Article
TY - JOUR
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
UR - http://www.scopus.com/inward/record.url?scp=85065103063&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85065103063&partnerID=8YFLogxK
U2 - 10.1016/j.freeradbiomed.2019.04.035
DO - 10.1016/j.freeradbiomed.2019.04.035
M3 - Article
C2 - 31047988
AN - SCOPUS:85065103063
VL - 137
SP - 194
EP - 200
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -