Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β
Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-10-01
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| Series: | Redox Biology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231722001926 |
| _version_ | 1811267039918030848 |
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| author | Yingying Shu Chaochun Zou Yuqing Cai Qiangqiang He Xiaowei Wu Haibin Zhu Meiyu Qv Yunqi Chao Chengyun Xu Lanfang Tang Ximei Wu |
| author_facet | Yingying Shu Chaochun Zou Yuqing Cai Qiangqiang He Xiaowei Wu Haibin Zhu Meiyu Qv Yunqi Chao Chengyun Xu Lanfang Tang Ximei Wu |
| author_sort | Yingying Shu |
| collection | DOAJ |
| description | Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3β (GSK3β) at Cys14, which activated GSK3β and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3β in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3β and subsequent GSK3β activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females. |
| first_indexed | 2024-04-12T20:55:19Z |
| format | Article |
| id | doaj.art-f05bb5293ebc4f0291eeaafc12a0200b |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-12T20:55:19Z |
| publishDate | 2022-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-f05bb5293ebc4f0291eeaafc12a0200b2022-12-22T03:17:01ZengElsevierRedox Biology2213-23172022-10-0156102420Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3βYingying Shu0Chaochun Zou1Yuqing Cai2Qiangqiang He3Xiaowei Wu4Haibin Zhu5Meiyu Qv6Yunqi Chao7Chengyun Xu8Lanfang Tang9Ximei Wu10Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, ChinaDepartment of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; Corresponding author. Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, 3333 Binsheng Road, Hangzhou, 310053, China.Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, ChinaDepartment of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, ChinaDepartment of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, ChinaDepartment of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; National Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, ChinaNational Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, China; Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, ChinaNational Clinical Research Center for Child Health, The Children's Hospital of Zhejiang University School of Medicine, Hangzhou, 310053, ChinaDepartment of Pharmacology, Zhejiang University School of Medicine, Hangzhou, 310058, China; Corresponding author. Department of Pharmacology, Zhejiang University School of Medicine, 866 Yuhangtang Road, Hangzhou, 310058, China.Vitamin C (VC, l-ascorbic acid) is an essential nutrient that plays a key role in metabolism and functions as a potent antioxidant in regulating the S-nitrosylation and denitrosylation of target proteins. The precise function of VC deprivation in glucose homeostasis is still unknown. In the absence of L-gulono-1,4-lactone oxidoreductase, an essential enzyme for the last step of VC synthesis, VC deprivation resulted in persistent hypoglycemia and subsequent impairment of cognitive functions in female but not male mouse pups. The cognitive disorders caused by VC deprivation were largely reversed when these female pups were given glucose. VC deprivation-induced S-nitrosylation of glycogen synthase kinase 3β (GSK3β) at Cys14, which activated GSK3β and inactivated glycogen synthase to decrease glycogen synthesis and storage under the feeding condition, while VC deprivation inactivated glycogen phosphorylase to decrease glycogenolysis under the fasting condition, ultimately leading to hypoglycemia and cognitive disorders. Treatment with Nω-Nitro-l-arginine methyl ester (l-NAME), a specific inhibitor of nitric oxide synthase, on the other hand, effectively prevented S-nitrosylation and activation of GSK3β in female pups in response to the VC deprivation and reversed hypoglycemia and cognitive disorders. Overall, this research identifies S-nitrosylation of GSK3β and subsequent GSK3β activation as a previously unknown mechanism controlling glucose homeostasis in female pups in response to VC deprivation, implying that VC supplementation in the prevention of hypoglycemia and cognitive disorders should be considered in the certain groups of people, particularly young females.http://www.sciencedirect.com/science/article/pii/S2213231722001926VCGSK3βS-nitrosylationHypoglycemiaCognitive disorder |
| spellingShingle | Yingying Shu Chaochun Zou Yuqing Cai Qiangqiang He Xiaowei Wu Haibin Zhu Meiyu Qv Yunqi Chao Chengyun Xu Lanfang Tang Ximei Wu Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β Redox Biology VC GSK3β S-nitrosylation Hypoglycemia Cognitive disorder |
| title | Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β |
| title_full | Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β |
| title_fullStr | Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β |
| title_full_unstemmed | Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β |
| title_short | Vitamin C deficiency induces hypoglycemia and cognitive disorder through S-nitrosylation-mediated activation of glycogen synthase kinase 3β |
| title_sort | vitamin c deficiency induces hypoglycemia and cognitive disorder through s nitrosylation mediated activation of glycogen synthase kinase 3β |
| topic | VC GSK3β S-nitrosylation Hypoglycemia Cognitive disorder |
| url | http://www.sciencedirect.com/science/article/pii/S2213231722001926 |
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