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Advanced glycation end-product-inhibited cell proliferation and protein expression of beta-catenin and cyclin D1 are dependent on glycogen synthase kinase 3beta in LLC-PK1 cells |
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| Authors: | Lin Kuan-Hua Guh Jinn-Yuh Mo Jen-Fong Chiou Shean-Jaw Hwang Chi-Ching Chuang Lea-Yea |
| Affiliation: | a Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan b Department of Internal Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan c Department of Biochemistry, Faculty of Medicine, Kaohsiung Medical University, 100 Zihyou 1st Road, Kaohsiung 807, Taiwan d Department of Medical Technology, School of Medical and Health Sciences, Fooyin University, Kaohsiung, Taiwan |
| Abstract: | Glycogen synthase kinase 3β (GSK3β) is increased by high glucose in mesangial cells. Thus, we studied the role of GSK3β in advanced glycation end-product (AGE)-induced effects in the proximal tubule-like LLC-PK1 cells. We found that AGE (100 μg/ml) time-dependently (8-48 h) increased phospho-GSK3β-Tyr216 (active GSK3β) and time-dependently (4-24 h) decreased phospho-GSK3β-Ser21/9 (inactive GSK3β) protein expression. Meanwhile, AGE (100 μg/ml) activated GSK3β kinase at 8-48 h. AGE (100 μg/ml) dose-dependently (75-100 μg/ml) decreased β-catenin protein expression but AGE did not decrease β-catenin protein expression until 48 h. SB216763 (a GSK3β inhibitor) and GSK3β shRNA attenuated AGE (100 μg/ml)-inhibited cell proliferation and protein expression of β-catenin and cyclin D1 at 48 h. SB216763 also attenuated AGE-induced type IV collagen. We conclude that AGE activates GSK3β in LLC-PK1 cells. AGE-inhibited β-catenin and cyclin D1 protein expression are dependent on GSK3β. Moreover, AGE-inhibited cell proliferation and AGE-induced type IV collagen protein expression are dependent on GSK3β. |
| Keywords: | Advanced glycation end-product Glycogen synthase kinase 3β β-Catenin Cyclin D1 |
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