Nitric oxide signaling in stretch‐induced apoptosis of neonatal rat cardiomyocytes
| العنوان: | Nitric oxide signaling in stretch‐induced apoptosis of neonatal rat cardiomyocytes |
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| المؤلفون: | Xudong Liao, Jun‐Ming Liu, Lei Du, Aihui Tang, Yingli Shang, Shi Qiang Wang, Lan‐Ying Chen, Quan Chen |
| المصدر: | The FASEB Journal. 20:1883-1885 |
| بيانات النشر: | Wiley, 2006. |
| سنة النشر: | 2006 |
| مصطلحات موضوعية: | Reflex, Stretch, medicine.medical_specialty, Programmed cell death, Thapsigargin, Nitric Oxide Synthase Type III, Nitric Oxide Synthase Type II, Apoptosis, Biology, Nitric Oxide, Biochemistry, Calcium in biology, chemistry.chemical_compound, Enos, Internal medicine, Genetics, medicine, Animals, Rats, Wistar, Molecular Biology, Calcium signaling, Muscle Cells, Cell Death, Ryanodine receptor, Myocardium, Heart, biology.organism_classification, Rats, NG-Nitroarginine Methyl Ester, Endocrinology, Animals, Newborn, chemistry, Guanylate Cyclase, Enzyme Induction, Hypertension, Signal transduction, Signal Transduction, Biotechnology |
| الوصف: | Pressure overload associated with hypertension is an important pathological factor leading to heart remodeling and ultimately heart failure partially due to cardiomyocyte apoptosis. Here we show that endogenous NO signaling plays a critical role in mechanical stretch-induced cardiomyocyte apoptosis. Mechanical stretch induced elevated expression of both eNOS and inducible NO synthase (iNOS) and increased synthesis of NO. A sustained increase in iNOS expression was also found in hearts of hypertensive rats in vivo. Blockade of NO signaling by inhibitors of NOS (L-NAME and AMT) or downstream guanylyl cyclase (ODQ) strongly inhibited stretch-induced apoptosis, mitochondria depolarization, and cytochrome c release, suggesting that NO is required in stretch-induced cardiomyocyte apoptosis. The expression of iNOS, but not eNOS, was blocked by L-NAME and ODQ, indicating that the iNOS induction is NO dependent. The initial elevation of NO is likely due to Ca(2+)-dependent activation of eNOS because elimination of intracellular calcium by EGTA-AM inhibited both iNOS induction and NO elevation. Other calcium signaling inhibitors (nifedipine, ryanodine, thapsigargin, and ionic gadolinium) also attenuated the initial NO elevation. These data indicate that mechanical signals initiate Ca(2+)-dependent NO synthesis, which is further amplified by activation of NO-induced iNOS expression, to regulate cardiomyocyte apoptosis. |
| تدمد: | 1530-6860 0892-6638 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::365b068994ee044cb08e6bb28d557a10 https://doi.org/10.1096/fj.06-5717fje |
| حقوق: | CLOSED |
| رقم الأكسشن: | edsair.doi.dedup.....365b068994ee044cb08e6bb28d557a10 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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