TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway
Hyperglycemia-induced neuronal apoptosis is one of the important reasons for diabetic neuropathy. Long-time exposure to high glucose accelerates many aberrant glucose metabolic pathways and eventually leads to neuronal injury. However, the underlying mechanisms of metabolic alterations remain unknow...
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Molecular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnmol.2019.00193/full |
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| author | Wenjuan Zhou Yuan Yao Jinxing Li Dong Wu Man Zhao Zongting Yan Aimei Pang Liang Kong |
| author_facet | Wenjuan Zhou Yuan Yao Jinxing Li Dong Wu Man Zhao Zongting Yan Aimei Pang Liang Kong |
| author_sort | Wenjuan Zhou |
| collection | DOAJ |
| description | Hyperglycemia-induced neuronal apoptosis is one of the important reasons for diabetic neuropathy. Long-time exposure to high glucose accelerates many aberrant glucose metabolic pathways and eventually leads to neuronal injury. However, the underlying mechanisms of metabolic alterations remain unknown. TP53-inducible glycolysis and apoptosis regulator (TIGAR) is an endogenous inhibitor of glycolysis and increases the flux of pentose phosphate pathway (PPP) by regulating glucose 6-phosphate dehydrogenase (G6PD). TIGAR is highly expressed in neurons, but its role in hyperglycemia-induced neuronal injury is still unclear. In this study, we observed that TIGAR and G6PD are decreased in the hippocampus of streptozotocin (STZ)-induced diabetic mice. Correspondingly, in cultured primary neurons and Neuro-2a cell line, stimulation with high glucose induced significant neuronal apoptosis and down-regulation of TIGAR expression. Overexpression of TIGAR reduced the number of TUNEL-positive neurons and prevented the activation of Caspase-3 in cultured neurons. Furthermore, enhancing the expression of TIGAR rescued high glucose-induced autophagy impairment and the decrease of G6PD. Nitric oxide synthase 1 (NOS1), a negative regulator of autophagy, is also inhibited by overexpression of TIGAR. Inhibition of autophagy abolished the protective effect of TIGAR in neuronal apoptosis in Neuro-2a. Importantly, overexpression of TIGAR in the hippocampus ameliorated STZ-induced cognitive impairment in mice. Therefore, our data demonstrated that TIGAR may have an anti-apoptosis effect via up-regulation of autophagy in diabetic neuropathy. |
| first_indexed | 2024-12-13T22:05:52Z |
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| id | doaj.art-158a9f2cdd1e4313b360363a7e4b3319 |
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| issn | 1662-5099 |
| language | English |
| last_indexed | 2024-12-13T22:05:52Z |
| publishDate | 2019-08-01 |
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| series | Frontiers in Molecular Neuroscience |
| spelling | doaj.art-158a9f2cdd1e4313b360363a7e4b33192022-12-21T23:29:50ZengFrontiers Media S.A.Frontiers in Molecular Neuroscience1662-50992019-08-011210.3389/fnmol.2019.00193470727TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy PathwayWenjuan Zhou0Yuan Yao1Jinxing Li2Dong Wu3Man Zhao4Zongting Yan5Aimei Pang6Liang Kong7Key Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Shandong University, Jinan, ChinaDepartment of Physical Education, Shanghai Normal University, Shanghai, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaKey Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Shandong University, Jinan, ChinaKey Laboratory of the Ministry of Education for Experimental Teratology, Shandong Provincial Key Laboratory of Mental Disorders, Department of Human Anatomy and Histoembryology, School of Basic Medical Sciences, Shandong University, Jinan, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaDepartment of Clinical Laboratory, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, ChinaHyperglycemia-induced neuronal apoptosis is one of the important reasons for diabetic neuropathy. Long-time exposure to high glucose accelerates many aberrant glucose metabolic pathways and eventually leads to neuronal injury. However, the underlying mechanisms of metabolic alterations remain unknown. TP53-inducible glycolysis and apoptosis regulator (TIGAR) is an endogenous inhibitor of glycolysis and increases the flux of pentose phosphate pathway (PPP) by regulating glucose 6-phosphate dehydrogenase (G6PD). TIGAR is highly expressed in neurons, but its role in hyperglycemia-induced neuronal injury is still unclear. In this study, we observed that TIGAR and G6PD are decreased in the hippocampus of streptozotocin (STZ)-induced diabetic mice. Correspondingly, in cultured primary neurons and Neuro-2a cell line, stimulation with high glucose induced significant neuronal apoptosis and down-regulation of TIGAR expression. Overexpression of TIGAR reduced the number of TUNEL-positive neurons and prevented the activation of Caspase-3 in cultured neurons. Furthermore, enhancing the expression of TIGAR rescued high glucose-induced autophagy impairment and the decrease of G6PD. Nitric oxide synthase 1 (NOS1), a negative regulator of autophagy, is also inhibited by overexpression of TIGAR. Inhibition of autophagy abolished the protective effect of TIGAR in neuronal apoptosis in Neuro-2a. Importantly, overexpression of TIGAR in the hippocampus ameliorated STZ-induced cognitive impairment in mice. Therefore, our data demonstrated that TIGAR may have an anti-apoptosis effect via up-regulation of autophagy in diabetic neuropathy.https://www.frontiersin.org/article/10.3389/fnmol.2019.00193/fullhyperglycemiaTIGARneuronal apoptosisautophagyNOS1 |
| spellingShingle | Wenjuan Zhou Yuan Yao Jinxing Li Dong Wu Man Zhao Zongting Yan Aimei Pang Liang Kong TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway Frontiers in Molecular Neuroscience hyperglycemia TIGAR neuronal apoptosis autophagy NOS1 |
| title | TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway |
| title_full | TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway |
| title_fullStr | TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway |
| title_full_unstemmed | TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway |
| title_short | TIGAR Attenuates High Glucose-Induced Neuronal Apoptosis via an Autophagy Pathway |
| title_sort | tigar attenuates high glucose induced neuronal apoptosis via an autophagy pathway |
| topic | hyperglycemia TIGAR neuronal apoptosis autophagy NOS1 |
| url | https://www.frontiersin.org/article/10.3389/fnmol.2019.00193/full |
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