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首页> 外文期刊>The Korean Journal of Physiology & Pharmacology >Nitric Oxide-Induced Autophagy in MC3T3-E1 Cells is Associated with Cytoprotection via AMPK Activation
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Nitric Oxide-Induced Autophagy in MC3T3-E1 Cells is Associated with Cytoprotection via AMPK Activation

机译：一氧化氮诱导的自噬在MC3T3-E1细胞中通过AMPK激活与细胞保护相关。

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Nitric oxide (NO) is important in the regulation of bone remodeling, whereas high concentration of NO promotes cell death of osteoblast. However, it is not clear yet whether NO-induced autophagy is implicated in cell death or survival of osteoblast. The present study is aimed to examine the role of NO-induced autophagy in the MC3T3-E1 cells and their underlying molecular mechanism. The effect of sodium nitroprusside (SNP), an NO donor, on the cytotoxicity of the MC3T3-E1 cells was determined by MTT assay and expression of apoptosis or autophagy associated molecules was evaluated by western blot analysis. The morphological observation of autophagy and apoptosis by acridine orange stain and TUNEL assay were performed, respectively. Treatment of SNP decreased the cell viability of the MC3T3-E1 cells in dose- and time-dependent manner. SNP increased expression levels of p62, ATG7, Beclin-1 and LC3-II, as typical autophagic markers and augmented acidic autophagolysosomal vacuoles, detected by acridine orange staining. However, pretreatment with 3-methyladenine (3MA), the specific inhibitor for autophagy, decreased cell viability, whereas increased the cleavage of PARP and caspase-3 in the SNP-treated MC3T3-E1 cells. AMP-activated protein kinase (AMPK), a major autophagy regulatory kinase, was activated in SNP-treated MC3T3-E1 cells. In addition, pretreatment with compound C, an inhibitor of AMPK, decreased cell viability, whereas increased the number of apoptotic cells, cleaved PARP and caspase-3 levels compared to those of SNP-treated MC3T3-E1 cells. Taken together, it is speculated that NO-induced autophagy functions as a survival mechanism via AMPK activation against apoptosis in the MC3T3-E1 cells.
机译：一氧化氮（NO）在调节骨骼重塑中很重要，而高浓度的NO会促进成骨细胞死亡。但是，尚不清楚NO诱导的自噬是否与成骨细胞的细胞死亡或存活有关。本研究旨在检查NO诱导的自噬在MC3T3-E1细胞中的作用及其潜在的分子机制。通过MTT测定确定NO供体硝普钠（SNP）对MC3T3-E1细胞的细胞毒性的作用，并通过蛋白质印迹分析评估凋亡或自噬相关分子的表达。分别用a啶橙染色和TUNEL法观察自噬和凋亡的形态。 SNP的治疗以剂量和时间依赖性方式降低了MC3T3-E1细胞的细胞活力。 SNP增加了p62，ATG7，Beclin-1和LC3-II的表达水平，这是典型的自噬标记，并通过a啶橙染色检测到酸性自噬体液泡增加。但是，用3-甲基腺嘌呤（3MA）进行预处理，这是自噬的特异性抑制剂，降低了细胞活力，而增加了SNP处理的MC3T3-E1细胞中PARP和caspase-3的裂解。 AMP激活的蛋白激酶（AMPK）是一种主要的自噬调节激酶，在SNP处理的MC3T3-E1细胞中被激活。此外，与SNP处理的MC3T3-E1细胞相比，用AMPK抑制剂化合物C预处理可降低细胞活力，而增加凋亡细胞的数量，裂解PARP和caspase-3水平。两者合计，推测NO诱导的自噬通过AMPK激活作为抵抗MC3T3-E1细胞凋亡的生存机制。

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