Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways
Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) envi...
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| Format: | Article |
| Language: | English |
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Wiley
2016-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2016/6384759 |
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| author | Hsiao-Ya Tsai Chih-Pei Lin Po-Hsun Huang Szu-Yuan Li Jia-Shiong Chen Feng-Yen Lin Jaw-Wen Chen Shing-Jong Lin |
| author_facet | Hsiao-Ya Tsai Chih-Pei Lin Po-Hsun Huang Szu-Yuan Li Jia-Shiong Chen Feng-Yen Lin Jaw-Wen Chen Shing-Jong Lin |
| author_sort | Hsiao-Ya Tsai |
| collection | DOAJ |
| description | Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. |
| format | Article |
| id | doaj-art-e261d62db3974c6fa4f354fb8cfcd470 |
| institution | DOAJ |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2016-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of Diabetes Research |
| spelling | doaj-art-e261d62db3974c6fa4f354fb8cfcd4702025-08-20T03:21:07ZengWileyJournal of Diabetes Research2314-67452314-67532016-01-01201610.1155/2016/63847596384759Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase PathwaysHsiao-Ya Tsai0Chih-Pei Lin1Po-Hsun Huang2Szu-Yuan Li3Jia-Shiong Chen4Feng-Yen Lin5Jaw-Wen Chen6Shing-Jong Lin7Institute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanDepartment of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanInstitute and Department of Pharmacology, National Yang-Ming University, Taipei, TaiwanDepartment of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, TaiwanDivision of Cardiology, Taipei Veterans General Hospital, Taipei, TaiwanInstitute of Clinical Medicine, National Yang-Ming University, Taipei, TaiwanCoenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.http://dx.doi.org/10.1155/2016/6384759 |
| spellingShingle | Hsiao-Ya Tsai Chih-Pei Lin Po-Hsun Huang Szu-Yuan Li Jia-Shiong Chen Feng-Yen Lin Jaw-Wen Chen Shing-Jong Lin Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways Journal of Diabetes Research |
| title | Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways |
| title_full | Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways |
| title_fullStr | Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways |
| title_full_unstemmed | Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways |
| title_short | Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways |
| title_sort | coenzyme q10 attenuates high glucose induced endothelial progenitor cell dysfunction through amp activated protein kinase pathways |
| url | http://dx.doi.org/10.1155/2016/6384759 |
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