Dataset Information

Female adult mouse cardiomyocytes are protected against oxidative stress.

ABSTRACT: Premenopausal women have less cardiovascular disease and lower cardiovascular morbidity and mortality than men the same age. Our previous studies showed that female mice have lower mortality and better preserved cardiac function after myocardial infarction. However, the precise cellular and molecular mechanisms responsible for such a sex difference are not well established. Using cultured adult mouse cardiomyocytes, we tested the hypothesis that the survival advantage of females stems from activated estrogen receptors and Akt survival signaling pathways. Adult mouse cardiomyocytes were isolated from male and female C57BL/6J mice and treated with hydrogen peroxide (100 micromol/L) for 30 minutes. Cell survival was indicated by rod ratio (rod shaped cells:total cells), cell death by lactate dehydrogenase release, and positive staining of annexin-V (a marker for apoptosis) and propidium iodide (a marker for necrosis). In response to hydrogen peroxide(,) female adult mouse cardiomyocytes exhibited a higher rod ratio, lower lactate dehydrogenase release, and fewer Annexin-V-positive and propidium iodide-positive cells compared with males. Phospho-Akt was greater in females both at baseline and after hydrogen peroxide stimulation. The downstream molecule of Akt, phosphor-GSK-3beta (inactivation), was also higher, whereas caspase 3 activity was lower in females in response to hydrogen peroxide. Bcl-2 did not differ between sexes. Estrogen receptor-alpha was the dominant isoform in females, whereas estrogen receptor-beta was low but similar in both sexes. Our findings demonstrate that female adult mouse cardiomyocytes have a greater survival advantage when challenged with oxidative stress-induced cell death. This may be attributable to activation of Akt and inhibition of GSK-3beta and caspase 3 through an estrogen receptor-alpha-mediated mechanism.

SUBMITTER: Wang F

PROVIDER: S-EPMC2861855 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Female adult mouse cardiomyocytes are protected against oxidative stress.

Wang Fangfei F He Quan Q Sun Ying Y Dai Xiangguo X Yang Xiao-Ping XP

Hypertension (Dallas, Tex. : 1979) 20100308 5

Premenopausal women have less cardiovascular disease and lower cardiovascular morbidity and mortality than men the same age. Our previous studies showed that female mice have lower mortality and better preserved cardiac function after myocardial infarction. However, the precise cellular and molecular mechanisms responsible for such a sex difference are not well established. Using cultured adult mouse cardiomyocytes, we tested the hypothesis that the survival advantage of females stems from activ ...[more]

PMID: 20212261

Similar Datasets

Project description:Diastolic heart failure (HF) i.e., "HF with preserved ejection fraction" (HF-preserved EF) accounts for up to 50% of all HF presentations; however there have been no therapeutic advances. This stems in part from an incomplete understanding about HF-preserved EF. Hypertension is the major cause of HF-preserved EF whilst HF-preserved EF is also highly associated with obesity. Similarly, excessive reactive oxygen species (ROS), i.e., oxidative stress occurs in hypertension and obesity, sensitizing the heart to the renin-angiotensin-aldosterone system, inducing autophagic type-II programmed cell death and accelerating the propensity to adverse cardiac remodeling, diastolic dysfunction and HF. Adiponectin (APN), an adipokine, mediates cardioprotective actions but it is unknown if APN modulates cardiomyocyte autophagy. We tested the hypothesis that APN ameliorates oxidative stress-induced autophagy in cardiomyocytes. Isolated adult rat ventricular myocytes were pretreated with recombinant APN (30 µg/mL) followed by 1mM hydrogen peroxide (H2O2) exposure. Wild type (WT) and APN-deficient (APN-KO) mice were infused with angiotensin (Ang)-II (3.2 mg/kg/d) for 14 days to induced oxidative stress. Autophagy-related proteins, mTOR, AMPK and ERK expression were measured. H2O2 induced LC3I to LC3II conversion by a factor of 3.4±1.0 which was abrogated by pre-treatment with APN by 44.5±10%. However, neither H2O2 nor APN affected ATG5, ATG7, or Beclin-1 expression. H2O2 increased phospho-AMPK by 49±6.0%, whilst pretreatment with APN decreased phospho-AMPK by 26±4%. H2O2 decreased phospho-mTOR by 36±13%, which was restored by APN. ERK inhibition demonstrated that the ERK-mTOR pathway is involved in H2O2-induced autophagy. Chronic Ang-II infusion significantly increased myocardial LC3II/I protein expression ratio in APN-KO vs. WT mice. These data suggest that excessive ROS caused cardiomyocyte autophagy which was ameliorated by APN by inhibiting an H2O2-induced AMPK/mTOR/ERK-dependent mechanism. These findings demonstrate the anti-oxidant potential of APN in oxidative stress-associated cardiovascular diseases, such as hypertension-induced HF-preserved EF.

Dataset Information

Female adult mouse cardiomyocytes are protected against oxidative stress.

Publications

Female adult mouse cardiomyocytes are protected against oxidative stress.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets