首页|高糖经由ROS或TGF-β1/PI3K/Akt信号途径促进肺腺癌A549细胞HO-1表达增加

高糖经由ROS或TGF-β1/PI3K/Akt信号途径促进肺腺癌A549细胞HO-1表达增加

High Glucose Promotes Heme Oxygenase-1 Expression in Human Lung Epithelial Cells via Reactive Oxygen Species or TGF-~/PI3K/Akt Signaling Pathway

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目的 探讨高糖对肺腺癌A549细胞血红素加氧酶-1(HO-1)表达的影响及机制.方法 应用Westernblot技术和逆转录PCR技术检测高糖对人肺腺癌上皮细胞系A549细胞HO-1的表达.应用酶联免疫吸附试验检测HO-1酶活性和氧化应激产物.结果 用25 mmol/L高糖处理肺A549细胞0、24、48、72 h,以及用5、10、25、40mmol/L葡萄糖处理A549细胞48 h,在蛋白水平和RNA水平,高糖诱导肺A549细胞HO-1表达呈浓度和时间依赖性.高糖诱导A549细胞活性氧(ROS)和转化生长因子β1(TGF-β1)产生增加,并介导HO-1表达增加.伴随HO-1表达增加,HO-1酶活性也相应增加.抗氧化剂N-乙酰半胱氨酸(NAC)和PI3K/Akt抑制剂可抑制高糖诱导的肺上皮细胞HO-1表达.结论高糖促进肺上皮细胞ROS和TGF-β1产生,介导HO-1表达增加,并伴随HO-1酶活性增加.
Objective To investigate the expression ofheme oxygenase-1 (HO-1) by high glucose treatment in human lung epithelial A549 cells.Methods The effect of high glucose on the expression of HO-1 in A549 cells was investigated with Western blot and reverse transcription PCR.HO-1 enzymic activity and reactive oxygen species (ROS) production were investigated with enzyme-linked immunosorbent test.Results Treatment with 25 mmol/L high glucose for 0,24 h,48 h,72 h and in concentrations of 5 mmol/L,10 mmol/L,25 mmol/L,40 mmol/L for 48 h induced increased expression on protein and mRNA level of HO-1 in a concentration-and time-dependent manner in A549 cells.High glucose treatment increased production of ROS and transforming growth factor-β1 (TGF-β1) in A549 cells,which thus mediated HO-1 expression.Following the increase in HO-1 expression,the enzymatic activity of rO-1 also increased in high glucose-treated cells.Pretreatment with N-acetyl-L-cysteine (NAC) and PI3K/Akt inhibitors attenuated the high glucose-induced increased HO-1 expression.Conclusions High glucose increases ROS and TGF-β1 production in A549 cells,which mediates HO-1 expression and increases HO-1 enzymic activity.

Heme oxygenase-1Human lung epithelial cellsHigh glucoseReactive oxygen species

康小文、孔凡武、张薇、王欣燕、黄坤、李兆国、吴晓梅

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哈尔滨医科大学附属二院呼吸科 哈尔滨150086

哈尔滨医科大学附属二院肾内科 哈尔滨150086

哈尔滨医科大学附属一院呼吸科 哈尔滨150086

血红素加氧酶-1 人肺上皮细胞 高糖 活性氧

黑龙江省教育厅科研课题

12541563

2017

中国呼吸与危重监护杂志
四川大学华西医学中心,四川大学华西医院

中国呼吸与危重监护杂志

CSTPCDCSCD北大核心
影响因子:1.306
ISSN:1671-6205
年,卷(期):2017.16(1)
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