CO-Releasing Molecule-2 Prevents Acute Kidney Injury through Suppression of ROS-Fyn-ER Stress Signaling in Mouse Model
- 주제(기타) Cell Biology
- 설명문(일반) [Uddin, Md Jamal; Jeong, Jeewon; Pak, Eun Seon; Ha, Hunjoo] Ewha Womans Univ, Grad Sch Pharmaceut Sci, Coll Pharm, Seoul, South Korea
- 등재 SCIE, SCOPUS
- 발행기관 HINDAWI LTD
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182298
- 본문언어 영어
- Published As http://dx.doi.org/10.1155/2021/9947772
초록/요약
Acute kidney injury (AKI) most commonly appears in critically ill patients in hospitals. AKI is characterized as a quick deterioration of kidney function and has recently been identified to be tightly interlinked with chronic kidney diseases. The emerging major mediators of AKI include oxidative stress and endoplasmic reticulum (ER) stress. Carbon monoxide (CO) attenuates oxidative stress and ER stress in various cells, while Fyn, a member of the Src kinase family, is activated by oxidative stress and contributes to ER stress in skeletal muscle. Considering these, the objective of the current research was to determine (i) the involvement of Fyn in ER stress-mediated AKI and (ii) the effect of CO-releasing molecule-2 (CORM2) on reactive oxygen species- (ROS-) Fyn-ER stress-mediated AKI. Pretreatment with CORM2 (30 mg/kg) efficiently inhibited LPS (30 mg/kg)-induced oxidative stress, inflammation, and cellular apoptosis during AKI in C57BL/6J mice. Also, CORM2 efficiently suppressed the activation of Fyn and ER stress in AKI mice. Consistently, pretreatment with CORM2 inhibited oxidative stress, Fyn activation, ER stress, inflammation, and apoptosis in LPS- or H2O2-stimulated proximal epithelial tubular cells. Fyn inhibition using siRNA or an inhibitor (PP2) significantly attenuated ER stress responses in the cells. These data suggest that CORM2 may become a potential treatment option against ROS-Fyn-ER stress-mediated AKI.
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