Anti-Proliferative Effects of Rutin on OLETF Rat Vascular Smooth Muscle Cells Stimulated by Glucose Variability
| Autor: | Seong Jin Lee, Young Jung Cho, Sung Hoon Yu, Doo Man Kim, Hyung Joon Yoo, Jae Myung Yu, Dong Hyun Kang |
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| Rok vydání: | 2014 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway Male medicine.medical_specialty Vascular smooth muscle phosphatidylinositol 3-kinase p38 mitogen-activated protein kinases Rats Inbred OLETF Rutin Myocytes Smooth Muscle MAP Kinase Kinase 1 Biology p38 Mitogen-Activated Protein Kinases Muscle Smooth Vascular 03 medical and health sciences chemistry.chemical_compound Phosphatidylinositol 3-Kinases Endocrinology & Metabolism Cell Movement Internal medicine medicine Animals Rats Long-Evans Protein kinase A Protein kinase B Protein Kinase Inhibitors PI3K/AKT/mTOR pathway Cell Proliferation Flavonoids Mitogen-Activated Protein Kinase 3 Kinase Caspase 3 JNK Mitogen-Activated Protein Kinases NF-kappa B General Medicine Rats smooth muscle cells 030104 developmental biology Endocrinology Glucose chemistry mitogen-activated protein kinases Original Article hyperglycemia Reactive Oxygen Species |
| Zdroj: | Yonsei Medical Journal |
| ISSN: | 1976-2437 |
| Popis: | PURPOSE Proliferation of vascular smooth muscle cells (VSMCs) plays a crucial role in atherosclerosis. Rutin is a major representative of the flavonol subclass of flavonoids and has various pharmacological activities. Currently, data are lacking regarding its effects on VSMC proliferation induced by intermittent hyperglycemia. Here, we demonstrate the effects of rutin on VSMC proliferation and migration according to fluctuating glucose levels. MATERIALS AND METHODS Primary cultures of male Otsuka Long-Evans Tokushima Fatty (OLETF) rat VSMCs were obtained from enzymatically dissociated rat thoracic aortas. VSMCs were incubated for 72 h with alternating normal (5.5 mmol/L) and high (25.0 mmol/L) glucose media every 12 h. Proliferation and migration of VSMCs, the proliferative molecular pathway [including p44/42 mitogen-activated protein kinases (MAPK), mitogen-activated protein kinase kinase 1/2 (MEK1/2), p38 MAPK, phosphoinositide 3-kinase (PI3K), c-Jun N-terminal protein kinase (JNK), nuclear factor kappa B (NF-κB), and Akt], the migratory pathway (big MAPK 1, BMK1), reactive oxygen species (ROS), and apoptotic pathway were analyzed. RESULTS We found enhanced proliferation and migration of VSMCs when cells were incubated in intermittent high glucose conditions, compared to normal glucose. These effects were lowered upon rutin treatment. Intermittent treatment with high glucose for 72 h increased the expression of phospho-p44/42 MAPK (extracellular signal regulated kinase 1/2, ERK1/2), phospho-MEK1/2, phospho-PI3K, phospho-NF-κB, phospho-BMK1, and ROS, compared to treatment with normal glucose. These effects were suppressed by rutin. Phospho-p38 MAPK, phospho-Akt, JNK, and apoptotic pathways [B-cell lymphoma (Bcl)-xL, Bcl-2, phospho-Bad, and caspase-3] were not affected by fluctuations in glucose levels. CONCLUSION Fluctuating glucose levels increased proliferation and migration of OLETF rat VSMCs via MAPK (ERK1/2), BMK1, PI3K, and NF-κB pathways. These effects were inhibited by the antioxidant rutin. |
| Databáze: | OpenAIRE |
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