ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury
In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression....
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| Language: | English |
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China Science Publishing & Media Ltd.
2024-07-01
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| Series: | Acta Biochimica et Biophysica Sinica |
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| Online Access: | https://www.sciengine.com/doi/10.3724/abbs.2024120 |
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| author | Wu Qichao Xie Tingting Fu Chang Sun Chenyu Ma Yan Huang Zhengzhe Yang Jiao Li Xiaoxiao Li Wenqian Miao Changhong |
| author_facet | Wu Qichao Xie Tingting Fu Chang Sun Chenyu Ma Yan Huang Zhengzhe Yang Jiao Li Xiaoxiao Li Wenqian Miao Changhong |
| author_sort | Wu Qichao |
| collection | DOAJ |
| description | In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal <sc>(5 mM)</sc> and high <sc>(25 mM)</sc> glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications. |
| format | Article |
| id | doaj-art-ba02ccc303ea4e2ca30f005e7bd40e4c |
| institution | OA Journals |
| issn | 1672-9145 |
| language | English |
| publishDate | 2024-07-01 |
| publisher | China Science Publishing & Media Ltd. |
| record_format | Article |
| series | Acta Biochimica et Biophysica Sinica |
| spelling | doaj-art-ba02ccc303ea4e2ca30f005e7bd40e4c2025-08-20T01:55:33ZengChina Science Publishing & Media Ltd.Acta Biochimica et Biophysica Sinica1672-91452024-07-015743744610.3724/abbs.202412020d259ccZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injuryWu Qichao0Xie Tingting1Fu Chang2Sun Chenyu3Ma Yan4Huang Zhengzhe5Yang Jiao6Li Xiaoxiao7Li Wenqian8Miao Changhong9["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China","Department of Anesthesiology, Zhongshan Hospital (Xiamen), Fudan University, Xiamen 361015, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai 200031, China","Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]["Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai 200031, China","Shanghai Key Laboratory of Perioperative Stress and Protection, Shanghai 200031, China"]In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and its effects on p53 and inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal <sc>(5 mM)</sc> and high <sc>(25 mM)</sc> glucose conditions. Protein and gene expression levels are assessed by western blot analysis and qPCR respectively, while ROS levels are measured via flow cytometry. ZIPK expression is manipulated using overexpression plasmids, siRNAs, and shRNAs. The effects of the ZIPK inhibitor TC-DAPK6 are evaluated in a diabetic rat model. Our results show that high glucose significantly upregulates ZIPK, STAT5A, p53, and NOS2 expressions in HUVECs, thus increasing oxidative stress. Silencing of STAT5A reduces p53 and NOS2 expressions and reactive oxygen species (ROS) accumulation. ZIPK is essential for high glucose-induced p53 expression and ROS accumulation, while silencing of ZIPK reverses these effects. Overexpression of ZIPK combined with STAT5A silencing attenuates glucose-induced alterations in p53 and NOS2 expression, thereby preventing cell damage. Coimmunoprecipitation reveals a direct interaction between ZIPK and STAT5A in the nucleus under high-glucose condition. In diabetic rats, TC-DAPK6 treatment significantly decreases ZIPK, p53, and NOS2 expressions. Our findings suggest that ZIPK plays a critical role in high glucose-induced vascular injury via STAT5A-mediated pathways, proposing that ZIPK is a potential therapeutic target for diabetic vascular complications.https://www.sciengine.com/doi/10.3724/abbs.2024120ZIPKSTAT5Ap53ROS accumulation |
| spellingShingle | Wu Qichao Xie Tingting Fu Chang Sun Chenyu Ma Yan Huang Zhengzhe Yang Jiao Li Xiaoxiao Li Wenqian Miao Changhong ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury Acta Biochimica et Biophysica Sinica ZIPK STAT5A p53 ROS accumulation |
| title | ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury |
| title_full | ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury |
| title_fullStr | ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury |
| title_full_unstemmed | ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury |
| title_short | ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury |
| title_sort | zipk collaborates with stat5a in p53 mediated ros accumulation in hyperglycemia induced vascular injury |
| topic | ZIPK STAT5A p53 ROS accumulation |
| url | https://www.sciengine.com/doi/10.3724/abbs.2024120 |
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