Publication date: Available online 18 February 2018
Source:Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
Author(s): Jun-Xia Zhang, Xin-Liang Qu, Peng Chu, Du-Jiang Xie, Lin-Lin Zhu, Yue-Lin Chao, Li Li, Jun-Jie Zhang, Shao-Liang Chen
Uncoupled endothelial nitric oxide synthase (eNOS) produces O2− instead of nitric oxide (NO). Earlier, we reported rapamycin, an autophagy inducer and inhibitor of cellular proliferation, attenuated low shear stress (SS) induced O2− production. Nevertheless, it is unclear whether autophagy plays a critical role in the regulation of eNOS uncoupling. Therefore, this study aimed to investigate the modulation of autophagy on eNOS uncoupling induced by low SS exposure. We found that low SS induced endothelial O2− burst, which was accompanied by reduced NO release. Furthermore, inhibition of eNOS by L-NAME conspicuously attenuated low SS-induced O2− releasing, indicating eNOS uncoupling. Autophagy markers such as LC3 II/I ratio, amount of Beclin1, as well as ULK1/Atg1 were increased during low SS exposure, whereas autophagic degradation of p62/SQSTM1 was markedly reduced, implying impaired autophagic flux. Interestingly, low SS-induced NO reduction could be reversed by rapamycin, WYE-354 or ATG5 overexpression vector via restoration of autophagic flux, but not by N-acetylcysteine or apocynin. eNOS uncoupling might be ascribed to autophagic flux blockade because phosphorylation of eNOS Thr495 by low SS or PMA stimulation was also regulated by autophagy. In contrast, eNOS acetylation was not found to be regulated by low SS and autophagy. Notably, although low SS had no influence on eNOS Ser1177 phosphorylation, whereas boosted eNOS Ser1177 phosphorylation by rapamycin were in favor of the eNOS recoupling through restoration of autophagic flux. Taken together, we reported a novel mechanism for regulation of eNOS uncoupling by low SS via autophagy-mediated eNOS phosphorylation, which is implicated in geometrical nature of atherogenesis.
from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/2o6bwgf
via IFTTT
Εγγραφή σε:
Σχόλια ανάρτησης (Atom)
Δημοφιλείς αναρτήσεις
-
Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
-
Related Articles Anatomic parameters of the sacral lamina for osteosynthesis in transverse sacral fractures. Surg Radiol Anat....
-
Background Hyperthyroidism is associated with increased thrombotic risk. As contact system activation through formation of neutrophil extrac...
-
BACKGROUND AND PURPOSE: Dengue is a common arboviral disease, which uncommonly involves the brain. There has been a recent surge in dengu...
-
Abstract Purpose Investigate in patients with metastatic and/or irresectable colorectal cancer treated with systemic treatment with cape...
-
Abstract Objectives (1) To illustrate and describe the main types of pancreatic surgery; (2) to discuss the normal findings after pancre...
-
Publication date: January 2017 Source: The Journal of Emergency Medicine, Volume 52, Issue 1 Author(s): Patricia Michelle Troxell Klingen...
-
In rural Kenya, traditional and faith healers provide an alternative pathway to health care, including mental health care. However, not much...
-
2016-12-10T02-17-59Z Source: Indo American Journal of Pharmaceutical Research R. Santosh Kumar*, T. Naga Satya Yagnesh. Solid dispersio...
Δεν υπάρχουν σχόλια:
Δημοσίευση σχολίου