In:
Oxidative Medicine and Cellular Longevity, Hindawi Limited, Vol. 2020 ( 2020-03-02), p. 1-15
Kurzfassung:
Endothelial cell damage caused by oxidative stress is widely considered to be a triggering event in atherosclerosis (AS). However, the specific effect elicited by autophagy in endothelial cells undergoing oxidative stress remains controversial, especially during end-stage autophagy. The inhibition of end-stage autophagy has been reported to increase cell pyroptosis and contribute to endothelial damage. Several studies have shown that microRNA-103 is involved in end-stage autophagy; however, its specific mechanism of action is not yet characterized. In this study, we addressed the regulatory role of miR-103 in autophagy during oxidative stress of endothelial cells. Hydrogen peroxide (H 2 O 2 ) treatment was used as an in vitro model of oxidative stress. MTS and ROS levels were measured to evaluate cell activity. qRT-PCR was used to detect the expression of miR-103. Autophagy was examined using western blot, immunofluorescence staining, and electron microscopy, while western blot analysis detected pyroptosis-related proteins. Results show that miR-103 expression decreased under oxidative stress. Further, miR-103 repressed transcription of Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3). The oxidative stress caused by H 2 O 2 caused cell damage from 2 hours ( P 〈 0.05 ) and increased the level of intracellular reactive oxygen species ( P 〈 0.05 ); at the same time, the damage could be further aggravated by the stimulation of bafA1 ( P 〈 0.05 ). Under the stimulation of H 2 O 2 , the expression of miR-103 decreased ( P 〈 0.05 ). However, high expression of miR-103 could reduce the accumulation of LC3II and P62 ( P 〈 0.05 ) by inhibiting the downstream target gene Bcl-2/adenovirus E1B 19 kDa interacting protein (BNIP3), thus reducing the occurrence of cell pyroptosis ( P 〈 0.05 ). This process could be blocked by end-stage autophagy inhibitor bafA1 ( P 〈 0.05 ), which further indicated that miR-103 affected cell injury by autophagy. On the contrary, the low expression of miR-103 promoted the accumulation of autophagy protein and increased the occurrence of pyroptosis ( P 〈 0.05 ). In conclusion, inhibition of miR-103 restrained end-stage of autophagy by regulating BNIP3, thus changing the occurrence of cell pyroptosis.
Materialart:
Online-Ressource
ISSN:
1942-0900
,
1942-0994
DOI:
10.1155/2020/8351342
Sprache:
Englisch
Verlag:
Hindawi Limited
Publikationsdatum:
2020
ZDB Id:
2455981-7
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