Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway
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....
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.920601/full |
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| author | Yang-Yang Gu Yang-Yang Gu Yang-Yang Gu Xiao-Hui Tan Xiao-Hui Tan Xiao-Hui Tan Wen-Peng Song Wen-Peng Song Wen-Peng Song Wei-Dong Song Wei-Dong Song Wei-Dong Song Yi-Ming Yuan Yi-Ming Yuan Yi-Ming Yuan Zhong-Cheng Xin Zhong-Cheng Xin Jia-Dong Wang Dong Fang Dong Fang Dong Fang Rui-Li Guan Rui-Li Guan Rui-Li Guan |
| author_facet | Yang-Yang Gu Yang-Yang Gu Yang-Yang Gu Xiao-Hui Tan Xiao-Hui Tan Xiao-Hui Tan Wen-Peng Song Wen-Peng Song Wen-Peng Song Wei-Dong Song Wei-Dong Song Wei-Dong Song Yi-Ming Yuan Yi-Ming Yuan Yi-Ming Yuan Zhong-Cheng Xin Zhong-Cheng Xin Jia-Dong Wang Dong Fang Dong Fang Dong Fang Rui-Li Guan Rui-Li Guan Rui-Li Guan |
| author_sort | Yang-Yang Gu |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-12T07:56:57Z |
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| id | doaj.art-82ad61c27dd240c790003805fcdb5269 |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T07:56:57Z |
| publishDate | 2022-06-01 |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-82ad61c27dd240c790003805fcdb52692022-12-22T00:32:17ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-06-011310.3389/fphar.2022.920601920601Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling PathwayYang-Yang Gu0Yang-Yang Gu1Yang-Yang Gu2Xiao-Hui Tan3Xiao-Hui Tan4Xiao-Hui Tan5Wen-Peng Song6Wen-Peng Song7Wen-Peng Song8Wei-Dong Song9Wei-Dong Song10Wei-Dong Song11Yi-Ming Yuan12Yi-Ming Yuan13Yi-Ming Yuan14Zhong-Cheng Xin15Zhong-Cheng Xin16Jia-Dong Wang17Dong Fang18Dong Fang19Dong Fang20Rui-Li Guan21Rui-Li Guan22Rui-Li Guan23Department of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaBeijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaDepartment of Dental Implant Center, Beijing Stomatological Hospital, School of Stomatology, Capital Medical University, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaBeijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaBeijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, ChinaMale Reproductive and Sexual Medicine, Department of Urology, The Second Hospital of Tianjin Medical University, Tianjin, ChinaInstitute of Urology, Tianjin Medical University, Tianjin, ChinaDepartment of Radiation Medicine, Institute of Systems Biomedicine, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaBeijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, ChinaDepartment of Urology, Peking University First Hospital, Beijing, ChinaInstitute of Urology, Peking University, Beijing, ChinaBeijing Key Laboratory of Urogenital Diseases (male) Molecular Diagnosis and Treatment Center, Beijing, ChinaBackground: 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.https://www.frontiersin.org/articles/10.3389/fphar.2022.920601/fullendothelial dysfunctionicariside Ⅱpalmitic acidSRPK1-Akt-eNOS signaling pathwaynitric oxide |
| spellingShingle | Yang-Yang Gu Yang-Yang Gu Yang-Yang Gu Xiao-Hui Tan Xiao-Hui Tan Xiao-Hui Tan Wen-Peng Song Wen-Peng Song Wen-Peng Song Wei-Dong Song Wei-Dong Song Wei-Dong Song Yi-Ming Yuan Yi-Ming Yuan Yi-Ming Yuan Zhong-Cheng Xin Zhong-Cheng Xin Jia-Dong Wang Dong Fang Dong Fang Dong Fang Rui-Li Guan Rui-Li Guan Rui-Li Guan Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway Frontiers in Pharmacology endothelial dysfunction icariside Ⅱ palmitic acid SRPK1-Akt-eNOS signaling pathway nitric oxide |
| title | Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway |
| title_full | Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway |
| title_fullStr | Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway |
| title_full_unstemmed | Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway |
| title_short | Icariside Ⅱ Attenuates Palmitic Acid-Induced Endothelial Dysfunction Through SRPK1-Akt-eNOS Signaling Pathway |
| title_sort | icariside ii attenuates palmitic acid induced endothelial dysfunction through srpk1 akt enos signaling pathway |
| topic | endothelial dysfunction icariside Ⅱ palmitic acid SRPK1-Akt-eNOS signaling pathway nitric oxide |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.920601/full |
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