3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species
There is accumulating evidence showing that apoptosis induced by endoplasmic reticulum (ER) stress plays a key role in pancreatic β cell dysfunction and insulin resistance. 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) is a multifunctional enzyme located in the endoplasmic reticulum (ER), which has been...
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| Format: | Article |
| Language: | English |
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Wiley
2020-01-01
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| Series: | Journal of Diabetes Research |
| Online Access: | http://dx.doi.org/10.1155/2020/3426902 |
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| author | Yang Li Xude Wang Baoyu Yang Haozhen Wang Zhenzhong Ma Ziyin Lu Xiuli Lu Bing Gao |
| author_facet | Yang Li Xude Wang Baoyu Yang Haozhen Wang Zhenzhong Ma Ziyin Lu Xiuli Lu Bing Gao |
| author_sort | Yang Li |
| collection | DOAJ |
| description | There is accumulating evidence showing that apoptosis induced by endoplasmic reticulum (ER) stress plays a key role in pancreatic β cell dysfunction and insulin resistance. 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) is a multifunctional enzyme located in the endoplasmic reticulum (ER), which has been previously shown to protect neuronal cells from ER stress-induced apoptosis. However, the role of DHCR24 in type 2 diabetes is only incompletely understood so far. In the present study, we induced ER stress by tunicamycin (TM) treatment and showed that infection of MIN6 cells with Ad-DHCR24-myc rendered these cells resistant to caspase-3-mediated apoptosis induced by TM, while cells transfected with siRNAs targeting DHCR24 were more sensitive to TM. Western blot analysis showed that TM treatment induced upregulation of Bip protein levels in both cells infected with Ad-LacZ (the control group) and Ad-DHCR24-myc, indicating substantial ER stress. Cells infected with Ad-LacZ exhibited a rapid and strong activation of ATF6 and p38, peaking at 3 h after TM exposure. Conversely, cells infected with Ad-DHCR24-myc showed a higher and more sustained activation of ATF6 and Bip than control cells. DHCR24 overexpression also inhibited the generation of intracellular reactive oxygen species (ROS) induced by ER stress and protected cells from apoptosis caused by treatment with both cholesterol and hydrogen peroxide. In summary, these data demonstrate, for the first time, that DHCR24 protects pancreatic β cells from apoptosis induced by ER stress. |
| format | Article |
| id | doaj-art-7d0d3f22f69147f3851b93c2d65d9c39 |
| institution | Kabale University |
| issn | 2314-6745 2314-6753 |
| language | English |
| publishDate | 2020-01-01 |
| publisher | Wiley |
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| series | Journal of Diabetes Research |
| spelling | doaj-art-7d0d3f22f69147f3851b93c2d65d9c392025-02-03T06:46:41ZengWileyJournal of Diabetes Research2314-67452314-67532020-01-01202010.1155/2020/342690234269023β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen SpeciesYang Li0Xude Wang1Baoyu Yang2Haozhen Wang3Zhenzhong Ma4Ziyin Lu5Xiuli Lu6Bing Gao7Department of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Biochemistry and Molecular Biology, Life Science School, Liaoning University, Shenyang 110036, ChinaDepartment of Cell Biology and Genetics, Shenyang Medical College, Shenyang 110034, ChinaThere is accumulating evidence showing that apoptosis induced by endoplasmic reticulum (ER) stress plays a key role in pancreatic β cell dysfunction and insulin resistance. 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) is a multifunctional enzyme located in the endoplasmic reticulum (ER), which has been previously shown to protect neuronal cells from ER stress-induced apoptosis. However, the role of DHCR24 in type 2 diabetes is only incompletely understood so far. In the present study, we induced ER stress by tunicamycin (TM) treatment and showed that infection of MIN6 cells with Ad-DHCR24-myc rendered these cells resistant to caspase-3-mediated apoptosis induced by TM, while cells transfected with siRNAs targeting DHCR24 were more sensitive to TM. Western blot analysis showed that TM treatment induced upregulation of Bip protein levels in both cells infected with Ad-LacZ (the control group) and Ad-DHCR24-myc, indicating substantial ER stress. Cells infected with Ad-LacZ exhibited a rapid and strong activation of ATF6 and p38, peaking at 3 h after TM exposure. Conversely, cells infected with Ad-DHCR24-myc showed a higher and more sustained activation of ATF6 and Bip than control cells. DHCR24 overexpression also inhibited the generation of intracellular reactive oxygen species (ROS) induced by ER stress and protected cells from apoptosis caused by treatment with both cholesterol and hydrogen peroxide. In summary, these data demonstrate, for the first time, that DHCR24 protects pancreatic β cells from apoptosis induced by ER stress.http://dx.doi.org/10.1155/2020/3426902 |
| spellingShingle | Yang Li Xude Wang Baoyu Yang Haozhen Wang Zhenzhong Ma Ziyin Lu Xiuli Lu Bing Gao 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species Journal of Diabetes Research |
| title | 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species |
| title_full | 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species |
| title_fullStr | 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species |
| title_full_unstemmed | 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species |
| title_short | 3β-Hydroxysteroid-Δ24 Reductase (DHCR24) Protects Pancreatic β Cells from Endoplasmic Reticulum Stress-Induced Apoptosis by Scavenging Excessive Intracellular Reactive Oxygen Species |
| title_sort | 3β hydroxysteroid δ24 reductase dhcr24 protects pancreatic β cells from endoplasmic reticulum stress induced apoptosis by scavenging excessive intracellular reactive oxygen species |
| url | http://dx.doi.org/10.1155/2020/3426902 |
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