Involvement of FoxO1, Sp1, and Nrf2 in Upregulation of Negative Regulator of ROS by 15d PGJ2 Attenuates H2O2 Induced IL 6 Expression in Rat Brain Astrocytes

ASIA unversity > 醫學暨健康學院 > 學士後獸醫學系 > 期刊論文 > Item 310904400/115498

請使用永久網址來引用或連結此文件: http://asiair.asia.edu.tw/ir/handle/310904400/115498

題名:	Involvement of FoxO1, Sp1, and Nrf2 in Upregulation of Negative Regulator of ROS by 15d PGJ2 Attenuates H2O2 Induced IL 6 Expression in Rat Brain Astrocytes
作者:	王震宇;Wang, Chen-Yu;楊建中;Yang, Chien-Chung;蕭立德;Hsiao, Li-Der;楊春茂;Yang, Chuen-Mao
貢獻者:	醫學暨健康學院學士後獸醫學系
關鍵詞:	15d-PGJ2;Hydrogen peroxide;IL-6;NADPH oxidase;NRROS;p47phox.
日期:	2022-02-01
上傳時間:	2023-03-29 02:26:48 (UTC+0)
出版者:	亞洲大學
摘要:	Excessive production of reactive oxygen species (ROS) by NADPH oxidase (Nox) resulted in inflammation. The negative regulator of ROS (NRROS) dampens ROS generation during inflammatory responses. 15-Deoxy-?12,14-prostaglandin J2 (15d-PGJ2) exhibits neuroprotective effects on central nervous system (CNS). However, whether 15d-PGJ2-induced NRROS expression was unknown in rat brain astrocytes (RBA-1). NRROS expression was determined by Western blot, RT/real-time PCR, and promoter activity assays. The signaling components were investigated using pharmacological inhibitors or specific siRNAs. The interaction between transcription factors and the NRROS promoter was investigated by chromatin immunoprecipitation assay. Upregulation of NRROS on the hydrogen peroxide (H2O2)-mediated ROS generation and interleukin 6 (IL-6) secretion was measured. 15d-PGJ2-induced NRROS expression was mediated through PI3K/Akt-dependent activation of Sp1 and FoxO1 and established the essential promoter regions. We demonstrated that 15d-PGJ2 activated PI3K/Akt and following by cooperation between phosphorylated nuclear FoxO1 and Sp1 to initiate the NRROS transcription. In addition, Nrf2 played a key role in NRROS expression induced by 15d-PGJ2 which was mediated through its phosphorylation. Finally, the NRROS stable clones attenuated the H2O2-induced ROS generation and expression of IL-6 through suppressing the Nox-2 activity. These results suggested that 15d-PGJ2-induced NRROS expression is mediated through a PI3K/Akt-dependent FoxO1 and Sp1 phosphorylation, and Nrf2 cascade, which suppresses ROS generation through attenuating the p47phox phosphorylation and gp91phox formation and IL-6 expression in RBA-1 cells. These results confirmed the mechanisms underlying 15d-PGJ2-induced NRROS expression which might be a potential strategy for prevention and management of brain inflammatory and neurodegenerative diseases.
顯示於類別:	[學士後獸醫學系] 期刊論文

文件中的檔案:

檔案	描述	大小	格式	瀏覽次數
index.html		0Kb	HTML	150	檢視/開啟

在ASIAIR中所有的資料項目都受到原著作權保護.

資料載入中.....