Dataset Information

Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-?-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway.

ABSTRACT: Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from Acanthopanax koreanum, acts as an enhancer of eNOS activity and NO production. IPA treatment induced eNOS phosphorylation and NO production, which was correlated with eNOS phosphorylation via the activation of JNK1/2, p38 MAPK, AMPK, and CaMKII. In addition, the induction of eNOS phosphorylation by IPA was attenuated by pharmacological inhibitor of MAPKs, AMPK, and CaMKII. Finally, IPA treatment prevented the adhesion of TNF-?-induced monocytes to endothelial cells and suppressed the TNF-?-stimulated ICAM-1 expression via activation of NF-?B, while treatment with L-NAME, the NOS inhibitor, reversed the inhibitory effect of IPA on TNF-?-induced ICAM-1 expression via activation of NF-?B. Taken together, these findings show that IPA protects against TNF-?-induced vascular endothelium dysfunction through attenuation of the NF-?B pathway by activating eNOS/NO pathway in endothelial cells.

SUBMITTER: Jin SW

PROVIDER: S-EPMC6888592 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Impressic Acid, a Lupane-Type Triterpenoid from <i>Acanthopanax koreanum</i>, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway.

Jin Sun Woo SW Pham Hoa Thi HT Choi Jae Ho JH Lee Gi Ho GH Han Eun Hee EH Cho Young Ho YH Chung Young Chul YC Kim Young Ho YH Jeong Hye Gwang HG

International journal of molecular sciences 20191116 22

Atherosclerosis is one of the most reported diseases worldwide, and extensive research and trials are focused on the discovery and utilizing for novel therapeutics. Nitric oxide (NO) is produced mainly by endothelial nitric oxide synthase (eNOS) and it plays a key role in regulating vascular function including systemic blood pressure and vascular inflammation in vascular endothelium. In this study hypothesized that Impressic acid (IPA), a component isolated from <i>Acanthopanax koreanum</i>, act ...[more]

PMID: 31744135

Similar Datasets

Project description:Background: Endothelial dysfunction is commonly accompanied by a reduced capacity for nitric oxide (NO) production and decreased NO sensitivity, playing a central role in numerous vascular diseases. Saturated free fatty acids are known to reduce NO production and then induce endothelial dysfunction. Alternative splicing participates in the regulation of cellular and tissular homeostasis and is highly regulated by serine-arginine protein kinase (SRPK1). The role of SRPK1 in the biology of endothelial cells remains elusive. Icariside Ⅱ (ICA Ⅱ) has been reported to have protective effects on endothelial function. However, the specific molecular mechanisms are still unknown. The purpose of this study is to explore the role of SRPK1 in the biology of endothelial cells and the underlying mechanism of ICA Ⅱ on palmitic acid (PA) induced endothelial dysfunction. Methods: Endothelial dysfunction was induced using PA in human umbilical vein endothelial cells (HUVECs). The expression and phosphorylation of related proteins in the SRPK1-Akt-eNOS signaling pathway were detected by Western Blot. Cell Counting Kit-8 assay and Ki-67 immunofluorescence were used to estimate cell viability. Endothelial cell function was assessed by detecting NO production using DAF-FM DA. Interaction between ICA Ⅱ and SRPK1 was demonstrated by a biotinylated protein interaction pull-down assay. Results: The expressions of eNOS, Akt, and SRPK1 were down-regulated in the endothelial dysfunction stimulated by PA. SRPK1 inhibitor SPHINX31 restrained endothelial cell viability in a dose-dependent manner. Moreover, inhibition of SRPK1 using SPHINX31 and knockdown of SRPK1 by shRNA also showed a down-regulation of the proteins associated with the SRPK1-Akt-eNOS signaling pathway. Biotinylated protein interaction pull-down assay revealed that ICA Ⅱ could be directly bound with SRPK1. On the other hand, ICA Ⅱ could attenuate the PA-induced endothelial dysfunction and restore cell viability through the SRPK1-Akt-eNOS pathway. Conclusions: ICA Ⅱ, bound with SRPK1, could attenuate the endothelial dysfunction induced by the PA in HUVECs via the SRPK1-Akt-eNOS signaling pathway.

Dataset Information

Impressic Acid, a Lupane-Type Triterpenoid from Acanthopanax koreanum, Attenuates TNF-?-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway.

Publications

Impressic Acid, a Lupane-Type Triterpenoid from <i>Acanthopanax koreanum</i>, Attenuates TNF-α-Induced Endothelial Dysfunction via Activation of eNOS/NO Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets