Apamin inhibits THP-1-derived macrophage apoptosis via mitochondria-related apoptotic pathway

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• 作者：Soo-Jung Kim^a ; Ji-Hyun Park^a ; Kyung-Hyun Kim^a ; Woo-Ram Lee^a ; Hyun-Jin An^a ; Bo-Kyung Min^b ; Sang-Mi Han^c ; Kee-Sik Kim^d ; Kwan-Kyu Park^a ; ^{kkpark@cu.ac.kr}
• 关键词：Atherosclerosis ; Apoptosis ; Apamin ; oxLDL
• 刊名：Experimental and Molecular Pathology
• 出版年：2012
• 期刊代码：291_00144800
• 类别：med
• 出版时间：August, 2012
• 卷：93
• 期：1
• 页码：129-134
• 文件大小：720 K

摘要

The development of atherosclerotic lesions is mainly due to macrophage death. The oxidative stresses of monocytes/macrophages play a vital role in the initiation and amplification of atherosclerosis. Apamin, a component of bee venom, exerts an anti-inflammatory effect, and selectively inhibits the Ca^2 +-activated K⁺ channels. The mechanisms involved in the inhibition of macrophage apoptosis have been fully elucidated.

We induced oxidized low-density lipoprotein (oxLDL) in THP-1-derived macrophage and studied the effect of apamin on intercellular lipid levels, mitochondria-related apoptotic pathway and numbers of apoptotic cells.

Oil-red O staining indicates that the inhibition of apamin in the condition significantly prevents intracellular lipid deposition. Treatment with apamin significantly decreased the apoptotic macrophages by decreasing the expression of pro-apoptotic genes Bax, caspase-3 and PARP protein levels, as well as through increasing expression of anti-apoptotic genes Bcl-2 and Bcl-xL protein levels in the absence and presence of oxLDL. In vivo, with apamin treatment reduced apoptotic cells death by TUNEL staining.

These results indicate that apamin plays an important role in monocyte/macrophage apoptotic processing, which may provide a potential drug for preventing atherosclerosis.