Inhibition of SIRT6 aggravates p53-mediated ferroptosis in acute lung injury in mice

Cao, Yuanyuan; Peng, Tian; Ai, Chenmu; Li, Zhiwang; Lei, Xiaobao; Li, Guicheng; Li, Tao; Wang, Xiang; Cai, Shumin

doi:10.1016/j.heliyon.2023.e22272

Cited by 2 publications

(1 citation statement)

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“…De ciency of SIRT6 leads to cardiomyocyte injury and mitochondrial dysfunction, whereas its overexpression attenuates various cardiovascular diseases, suggesting that it plays an indispensable role in cardiomyocyte viability (Divya et al, 2024). A particular study showed that that inhibiting the expression of SIRT6 protein exacerbates iron death mediated by P53 in acute lung injury in mice, while inhibition of P53 attenuates the exacerbation of iron death injury by inhibiting SIRT6 expression (Cao et al, 2023b). To explore the relationship between sirt6 and ferroptosis, we measured the expression of ferroptosis-related proteins.…”

Section: Discussionmentioning

confidence: 99%

Gastrodin prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6

Wu,

Miao,

Cao

et al. 2024

Preprint

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Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation (SD)-induced cardiac injury and the mechanisms are unknown. This study established SD mice model using a modified multiple platform water method and induced ferroptosis model in H9C2 cells using Erastin. The heart rate of mice was measured, and myocardial and mitochondrial structures were visualized using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Myocardial injury, oxidative stress indicators and, Fe2+ levels were detected by the kit method. The reactive oxygen species (ROS) levels were detected by immunofluorescence, and SIRT6 and ferroptosis-associated protein expression levels were detected by Western blot. Reduced heart rate and abnormalities in myocardial tissue and mitochondrial structure were ameliorated in the SD group of mice after GAS treatment. GAS treatment reduced ROS levels in Erastin-induced H9c2 cells. GAS treatment reduced atrial natriuretic peptide (ANP), creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MAD), and Fe2+ levels, and increased superoxide dismutase (SOD) and glutathione (GSH) levels in the SD and Erastin groups. Western blot showed that GAS treatment increased the expression of sirtuin 6 (SIRT6), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) and decreased the expression of P53 in SD and Erastin groups. The SIRT6 inhibitor OSS_128167 (OSS) reversed GAS treatment of Erastin-induced ferroptosis in H9C2 cells. These observations propose that GAS prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6.

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Section: Discussionmentioning

confidence: 99%