التفاصيل البيبلوغرافية
| العنوان: |
Disrupting KATP channels diminishes the estrogen-mediated protection in female mutant mice during ischemia-reperfusion |
| المؤلفون: |
Gao, Jianjiong, Xu, Dong, Sabat, Grzegorz, Valdivia, Hector, Xu, Wei, Shi, Nian-Qing |
| بيانات النشر: |
BioMed Central Ltd. |
| سنة النشر: |
2014 |
| المجموعة: |
BioMed Central |
| مصطلحات موضوعية: |
KATP channel, Sulfonylurea receptor, Myocardial infarction, Gender difference, Estrogen, Estrogen receptor, Glycosylation |
| الوصف: |
Background Estrogen has been shown to mediate protection in female hearts against ischemia-reperfusion (I-R) stress. Composed by a Kir6.2 pore and an SUR2 regulatory subunit, cardiac ATP-sensitive potassium channels (KATP) remain quiescent under normal physiological conditions but they are activated by stress stimuli to confer protection to the heart. It remains unclear whether KATP is a regulatory target of estrogen in the female-specific I-R signaling pathway. In this study, we aimed at delineating the molecular mechanism underlying estrogen modulation on KATP channel activity during I-R. Materials and methods We employed KATP knockout mice in which SUR2 is disrupted (SUR2KO) to characterize their I-R response using an in vivo occlusion model. To test the protective effects of estrogen, female mice were ovariectomized and implanted with 17β-estradiol (E2) or placebo pellets (0.1 μg/g/day, 21-day release) before receiving an I-R treatment. Comparative proteomic analyses were performed to assess pathway-level alterations between KO-IR and WT-IR hearts. Results and discussion Echocardiographic results indicated that KO females were pre-disposed to cardiac dysfunction at baseline. The mutant mice were more susceptible to I-R stress by having bigger infarcts (46%) than WT controls (31%). The observation was confirmed using ovariectomized mice implanted with E2 or placebo. However, the estrogen-mediated protection was diminished in KO hearts. Expression studies showed that the SUR2 protein level, but not RNA level, was up-regulated in WT-IR mice relative to untreated controls possibly via PTMs. Our antibodies detected different glycosylated SUR2 receptor species after the PNGase F treatment, suggesting that SUR2 could be modified by N-glycosylation. We subsequently showed that E2 could further induce the formation of complex-glycosylated SUR2. Additional time-point experiments revealed that I-R hearts had increased levels of N-glycosylated SUR2; and DPM1, the first committed step enzyme in the ... |
| نوع الوثيقة: |
report |
| اللغة: |
English |
| العلاقة: |
http://www.clinicalproteomicsjournal.com/content/11/1/19Test |
| الإتاحة: |
http://www.clinicalproteomicsjournal.com/content/11/1/19Test |
| حقوق: |
Copyright 2014 Gao et al.; licensee BioMed Central Ltd. |
| رقم الانضمام: |
edsbas.2D20447E |
| قاعدة البيانات: |
BASE |
