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Article: Sodium tanshinone IIA sulfonate protects against hyperhomocysteine-induced vascular endothelial injury via activation of NNMT/SIRT1-mediated NRF2/HO-1 and AKT/MAPKs signaling in human umbilical vascular endothelial cells

TitleSodium tanshinone IIA sulfonate protects against hyperhomocysteine-induced vascular endothelial injury via activation of NNMT/SIRT1-mediated NRF2/HO-1 and AKT/MAPKs signaling in human umbilical vascular endothelial cells
Authors
KeywordsHyperhomocysteinemia
Methylnicotinamide
Mitochondrial dysfunction
Nicotinamide
Oxidative stress
Vascular endothelial dysfunction
Issue Date2023
Citation
Biomedicine and Pharmacotherapy, 2023, v. 158, article no. 114137 How to Cite?
AbstractHomocysteine (Hcy) is one of the independent risk factors of cardiovascular disease. Sodium tanshinone IIA sulfonate (STS) is a hydrophilic derivate of tanshinone IIA which is the main active constitute of Chinese Materia Medica Salviae Miltiorrhizae Radix et Rhizoma, and exhibits multiple pharmacological activities. However, whether STS could prevent from Hcy-induced endothelial cell injury is unknown. We found that STS dramatically reversed Hcy-induced cell death concentration dependently in human umbilical vascular endothelial cells (HUVECs). STS ameliorated the endothelial cell cycle progression, proliferation and cell migratory function impaired by Hcy, which might be co-related to the inhibition of intracellular oxidative stress and mitochondrial dysfunction. STS also elevated the phosphorylation of AKT and MAPKs and protein expression of sirtuin1 (SIRT1), NRF2 and HO-1 which were suppressed by Hcy. The protective effect of STS against Hcy-induced endothelial cell toxicity was partially attenuated by PI3K, AKT, MEK, ERK, SIRT1, NRF2 and HO-1 inhibitors. Besides, knockdown of SIRT1 by its siRNA dramatically decreased the endothelial protective effect of STS accompanied with suppression of SIRT1, NRF2, HO-1 and phosphorylated AKT. The activation of AKT or NRF2 partially reversed SIRT1-knockdown impaired cyto-protective effect of STS against Hcy-induced cell injury. Furthermore, STS prevented from Hcy-induced intracellular nicotinamide N-methyltransferase (NNMT) reduction along with elevation of intracellular methylnicotinamide (MNA), and MNA enhanced STS protecting against Hcy induced endothelial death. Knockdown of NNMT reduced the protective effect of STS against Hcy induced endothelial cell injury. Collectively, STS presented potent endothelial protective effect against Hcy and the underlying molecular mechanisms were involved in the suppression of intracellular oxidative stress and mitochondria dysfunction by activation of AKT/MAPKs, SIRT1/NRF2/HO-1 and NNMT/MNA signaling pathways.
Persistent Identifierhttp://hdl.handle.net/10722/335893
ISSN
2023 Impact Factor: 6.9
2023 SCImago Journal Rankings: 1.493
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhou, Zhong Yan-
dc.contributor.authorShi, Wen Ting-
dc.contributor.authorZhang, Jing-
dc.contributor.authorZhao, Wai Rong-
dc.contributor.authorXiao, Ying-
dc.contributor.authorZhang, Kai Yu-
dc.contributor.authorMa, Jie-
dc.contributor.authorTang, Jing Yi-
dc.contributor.authorWang, Yu-
dc.date.accessioned2023-12-28T08:49:32Z-
dc.date.available2023-12-28T08:49:32Z-
dc.date.issued2023-
dc.identifier.citationBiomedicine and Pharmacotherapy, 2023, v. 158, article no. 114137-
dc.identifier.issn0753-3322-
dc.identifier.urihttp://hdl.handle.net/10722/335893-
dc.description.abstractHomocysteine (Hcy) is one of the independent risk factors of cardiovascular disease. Sodium tanshinone IIA sulfonate (STS) is a hydrophilic derivate of tanshinone IIA which is the main active constitute of Chinese Materia Medica Salviae Miltiorrhizae Radix et Rhizoma, and exhibits multiple pharmacological activities. However, whether STS could prevent from Hcy-induced endothelial cell injury is unknown. We found that STS dramatically reversed Hcy-induced cell death concentration dependently in human umbilical vascular endothelial cells (HUVECs). STS ameliorated the endothelial cell cycle progression, proliferation and cell migratory function impaired by Hcy, which might be co-related to the inhibition of intracellular oxidative stress and mitochondrial dysfunction. STS also elevated the phosphorylation of AKT and MAPKs and protein expression of sirtuin1 (SIRT1), NRF2 and HO-1 which were suppressed by Hcy. The protective effect of STS against Hcy-induced endothelial cell toxicity was partially attenuated by PI3K, AKT, MEK, ERK, SIRT1, NRF2 and HO-1 inhibitors. Besides, knockdown of SIRT1 by its siRNA dramatically decreased the endothelial protective effect of STS accompanied with suppression of SIRT1, NRF2, HO-1 and phosphorylated AKT. The activation of AKT or NRF2 partially reversed SIRT1-knockdown impaired cyto-protective effect of STS against Hcy-induced cell injury. Furthermore, STS prevented from Hcy-induced intracellular nicotinamide N-methyltransferase (NNMT) reduction along with elevation of intracellular methylnicotinamide (MNA), and MNA enhanced STS protecting against Hcy induced endothelial death. Knockdown of NNMT reduced the protective effect of STS against Hcy induced endothelial cell injury. Collectively, STS presented potent endothelial protective effect against Hcy and the underlying molecular mechanisms were involved in the suppression of intracellular oxidative stress and mitochondria dysfunction by activation of AKT/MAPKs, SIRT1/NRF2/HO-1 and NNMT/MNA signaling pathways.-
dc.languageeng-
dc.relation.ispartofBiomedicine and Pharmacotherapy-
dc.subjectHyperhomocysteinemia-
dc.subjectMethylnicotinamide-
dc.subjectMitochondrial dysfunction-
dc.subjectNicotinamide-
dc.subjectOxidative stress-
dc.subjectVascular endothelial dysfunction-
dc.titleSodium tanshinone IIA sulfonate protects against hyperhomocysteine-induced vascular endothelial injury via activation of NNMT/SIRT1-mediated NRF2/HO-1 and AKT/MAPKs signaling in human umbilical vascular endothelial cells-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.biopha.2022.114137-
dc.identifier.pmid36525817-
dc.identifier.scopuseid_2-s2.0-85144074644-
dc.identifier.volume158-
dc.identifier.spagearticle no. 114137-
dc.identifier.epagearticle no. 114137-
dc.identifier.eissn1950-6007-
dc.identifier.isiWOS:000904396500001-

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