Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors
Brain-pancreas relative protein (BPRP) is a novel protein that we found in our laboratory. Previously we demonstrated that it is involved in ischemia and depression. In light of the putative association between diabetes and clinical depression, and the selective expression of BPRP in brain and pancr...
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| Format: | Article |
| Language: | English |
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Elsevier
2008-01-01
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| Series: | Journal of Pharmacological Sciences |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1347861319315336 |
| _version_ | 1818539761818664960 |
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| author | Lu Tie Ying Xu Yan-Hua Lin Xiao-Hao Yao Hong-Li Wu Yu-Hua Li Zhu-Fang Shen He-Ming Yu Xue-Jun Li |
| author_facet | Lu Tie Ying Xu Yan-Hua Lin Xiao-Hao Yao Hong-Li Wu Yu-Hua Li Zhu-Fang Shen He-Ming Yu Xue-Jun Li |
| author_sort | Lu Tie |
| collection | DOAJ |
| description | Brain-pancreas relative protein (BPRP) is a novel protein that we found in our laboratory. Previously we demonstrated that it is involved in ischemia and depression. In light of the putative association between diabetes and clinical depression, and the selective expression of BPRP in brain and pancreas, the present study examined whether BPRP levels are affected by induction of diabetes by alloxan injection in rats and exposure to high glucose levels in PC12 cells. Western blot and immunohistochemical analyses revealed that BPRP levels were decreased in the hippocampal CA1 neurons of diabetic rats 4 and 8 weeks post-alloxan injection and in PC12 cells 48 h after exposure to high concentrations of glucose. BPRP protein levels were not affected by osmolarity control treatments with mannitol. Follow-up pharmacological experiments in PC12 cells revealed that glucose-induced BPRP down-regulation was markedly attenuated by the calpain inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) or calpeptin, but not the proteasome-specific inhibitor carbobenzoxy-Leu-Leu-leucinal (MG132). The ability of calpain inhibitors to specifically counter the effects of high glucose exposure on BPRP levels further suggests that BPRP and calpain activity may contribute to diabetes complications in the central nervous system. Keywords:: brain-pancreas relative protein, diabetes, high glucose, proteasome inhibitor, calpeptin |
| first_indexed | 2024-12-11T21:46:23Z |
| format | Article |
| id | doaj.art-ae17f056d3b04b7e87d510c9155e334f |
| institution | Directory Open Access Journal |
| issn | 1347-8613 |
| language | English |
| last_indexed | 2024-12-11T21:46:23Z |
| publishDate | 2008-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmacological Sciences |
| spelling | doaj.art-ae17f056d3b04b7e87d510c9155e334f2022-12-22T00:49:37ZengElsevierJournal of Pharmacological Sciences1347-86132008-01-0110612837Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain InhibitorsLu Tie0Ying Xu1Yan-Hua Lin2Xiao-Hao Yao3Hong-Li Wu4Yu-Hua Li5Zhu-Fang Shen6He-Ming Yu7Xue-Jun Li8Department of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, ChinaInstitute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xiannongtan Street, Beijing 100050, ChinaNational Research Institute for Family Planning, Beijing 100081, ChinaDepartment of Pharmacology, School of Basic Medical Sciences and State Key Laboratory of Natural & Biomimetic Drugs, Peking University, Beijing 100083, China; Corresponding author. xjli@bjmu.edu.cnBrain-pancreas relative protein (BPRP) is a novel protein that we found in our laboratory. Previously we demonstrated that it is involved in ischemia and depression. In light of the putative association between diabetes and clinical depression, and the selective expression of BPRP in brain and pancreas, the present study examined whether BPRP levels are affected by induction of diabetes by alloxan injection in rats and exposure to high glucose levels in PC12 cells. Western blot and immunohistochemical analyses revealed that BPRP levels were decreased in the hippocampal CA1 neurons of diabetic rats 4 and 8 weeks post-alloxan injection and in PC12 cells 48 h after exposure to high concentrations of glucose. BPRP protein levels were not affected by osmolarity control treatments with mannitol. Follow-up pharmacological experiments in PC12 cells revealed that glucose-induced BPRP down-regulation was markedly attenuated by the calpain inhibitors N-acetyl-Leu-Leu-norleucinal (ALLN) or calpeptin, but not the proteasome-specific inhibitor carbobenzoxy-Leu-Leu-leucinal (MG132). The ability of calpain inhibitors to specifically counter the effects of high glucose exposure on BPRP levels further suggests that BPRP and calpain activity may contribute to diabetes complications in the central nervous system. Keywords:: brain-pancreas relative protein, diabetes, high glucose, proteasome inhibitor, calpeptinhttp://www.sciencedirect.com/science/article/pii/S1347861319315336 |
| spellingShingle | Lu Tie Ying Xu Yan-Hua Lin Xiao-Hao Yao Hong-Li Wu Yu-Hua Li Zhu-Fang Shen He-Ming Yu Xue-Jun Li Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors Journal of Pharmacological Sciences |
| title | Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors |
| title_full | Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors |
| title_fullStr | Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors |
| title_full_unstemmed | Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors |
| title_short | Down-Regulation of Brain-Pancreas Relative Protein in Diabetic Rats and by High Glucose in PC12 Cells: Prevention by Calpain Inhibitors |
| title_sort | down regulation of brain pancreas relative protein in diabetic rats and by high glucose in pc12 cells prevention by calpain inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S1347861319315336 |
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