NIH-Monthly Seminar (February 28th- 엄광현 교수님) Dear NIH-Korean Scientists, We will have the 1st NIH-KSA seminar on
February 28th (Next Fri.) 1p.m. Lunch will be provided by Psomagen, Inc. We hope to see you there! 올해 첫번째 NIH-KSA세미나가 다음주 금요일 2월28일 1시에 있을 예정입니다. Psomagen, Inc이 점심 제공합니다. 여러분의 많은 참여 부탁드립니다. Time (강연시간): February 28th (Fri), 13:00-14:00 PM (45 min seminar, 15
min Q&A) 장소: NIH Bethesda Campus, Building
10, FAES Room 7 - B1C206 SPEAKER INFORMATION Name(성함): Gwang Hyeon Eom (엄광현) Position and Department (직장과 직함):
Department of Pharmacology Chonnam National University Medical
School, Gwangju, Korea Seminar Title (강연제목): S-Nitrosylation of histone deacetylase 2
by neuronal nitric oxide synthase as a mechanism for heart failure with
preserved ejection fraction Abstract (초록) Background - Although the clinical importance of heart failure with
preserved ejection fraction (HFpEF), which makes up half of heart failure, has
been extensively explored, most therapeutic regimens, including nitric oxide
(NO) donors, lack therapeutic benefit. Here we report that neuronal nitric
oxide synthase (nNOS, also known as NOS1) induces HFpEF by S-nitrosylation of
histone deacetylase 2 (HDAC2). Methods
– Two animal models of HFpEF—SAUNA (SAlty drinking water/Unilateral
Nephrectomy/Aldosterone) and mild transverse aortic constriction (TAC)
mice—were used for the study. Results
- Among the post-translational modifications tested, S-nitrosylation was
dramatically increased. Both models showed increased nNOS expression and NO
production, which resulted in the S-nitrosylation of HDAC2 C262/274. HFpEF was
alleviated in S-nitrosylation-resistant HDAC2 knock-in mice. Pharmacologic
intervention by either nNOS inhibition or HDAC2 denitrosylation attenuated
HFpEF. Conclusions - Our observations are the first to demonstrate a
completely new mechanistic aspect in HFpEF, which may provide a novel
therapeutic approach to HFpEF. Our results also provide evidence to explain the
ineffectiveness of conventional NO-enhancement trials for improving HFpEF.
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