Effect of 2-(4-aminophenyl)-7-methoxybenzothiazole on TNF-alpha and TNFR2 expression in human leukemia U937 cells
碩士 === 國立中山大學 === 生物醫學研究所 === 102 === The aim of this study was to explore the relation of tumor necrosis factor-α(TNF-α)-mediated death pathway to 2-(4-aminophenyl)- 7-methoxybenzothiazole (7-OMe-APBT)-induced death of human leukemia U937 cells. 7-OMe-APBT elicited apoptosis of U937 cells via caspa...
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| Format: | Others |
| Language: | zh-TW |
| Published: |
2014
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| Online Access: | http://ndltd.ncl.edu.tw/handle/u42fdu |
| Summary: | 碩士 === 國立中山大學 === 生物醫學研究所 === 102 === The aim of this study was to explore the relation of tumor necrosis factor-α(TNF-α)-mediated death pathway to 2-(4-aminophenyl)- 7-methoxybenzothiazole (7-OMe-APBT)-induced death of human leukemia U937 cells. 7-OMe-APBT elicited apoptosis of U937 cells via caspase-8/mitochondria-dependent death pathway. 7-OMe-APBT elicited up-regulation of TNF-α and TNFR2 expression through activation of p38 MAPK. p38 MAPK-induced c-Jun phosphorylation up-regulated TNFR2 promoter activity. SB202190 (p38 MAPK inhibitor) treatment abrogated 7-OMe-APBT effect on promoting TNFR2 promoter activity and mRNA level. On the other hand, 7-OMe-APBT induced increased TNF-α mRNA stability via protein phosphatase 2A catalytic subunit α(PP2Acα)-mediated tristetraprolin (TTP) degradation. Pretreatment with SB202190 abolished 7-OMe-APBT-induced PP2Acα and TNF-α up-regulation. PP2A inhibitor (Okadaic acid) attenuated the ability of 7-OMe-APBT to induce TNF-α up-regulation and TTP degradation. TTP over-expression suppressed 7-OMe-APBT-induced TNF-α up-regulation and restored the viability of 7-OMe-APBT-treated cells. Our data indicate that 7-OMe-APBT elicits TNF-α up-regulation via p38 MAPK/PP2Acα-mediated TTP down-regulation, and suggest that the TNF-α-mediated death pathway is involved in 7-OMe-APBT-induced death of U937 cells.
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