Inhibition of Reactive Oxygen Species/Extracellular Signal-Regulated Kinases Pathway by Pioglitazone Attenuates Advanced Glycation End Products-Induced Proliferation of Vascular Smooth Muscle Cells in Rats
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- Yuan Xiaochen
- Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou Department of Cardiology, Institute of Cardiovascular Medicine of Southeast University, Zhongda Hospital of Southeast University
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- Zhang Zhengang
- Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou
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- Gong Kaizheng
- Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou
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- Zhao Pei
- Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou
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- Qin Jianhua
- Department of Cardiology, Institute of Cardiovascular Disease of Southeast University, The First People's Hospital of Yangzhou
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- Liu Naifeng
- Department of Cardiology, Institute of Cardiovascular Medicine of Southeast University, Zhongda Hospital of Southeast University
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Advanced glycation end products (AGEs) have been shown to induce the proliferation of vascular smooth muscle cells (VSMCs) and contribute to atherogenesis and diabetes. In the present study, we investigated the effects of pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist, on AGE-induced rat VSMC growth and the underlying mechanism. In cultured rat VSMCs, AGE treatment induced VSMC proliferation in time- and dose-dependent manner, while down-regulated the expression of PPARγ. Pretreatment of pioglitazone not only prevented the down-regulation of PPARγ, but inhibited VSMC proliferation and prevented S-phase entry of cell via a G0–G1 block in the presence of AGEs. Western blotting analysis showed that AGE treatment potentiated to activate extracelluar signal-regulated kinases (ERK1/2) by the induction of intracellular reactive oxygen species (ROS) production, since ROS scavenger N-acetyl-L-cysteine pretreatment significantly inhibited AGE-induced ERK1/2 activation. Further, pretreatment with either N-acetyl-L-cysteine or the inhibitor of ERK1/2 activation suppressed AGE-induced proliferation of VSMCs, suggesting a role of ROS/ERK1/2 signaling. Notably, we demonstrated that pretreatment of pioglitazone significantly attenuated AGE-induced ROS and ERK1/2 activation. Collectively, these results suggest that pioglitazone inhibits AGE-induced VSMC proliferation via increasing PPARγ expression and inhibiting ROS/ERK1/2 signaling pathway.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 34 (5), 618-623, 2011
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282679601880704
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- NII論文ID
- 130000657770
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 11057823
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
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