Pyrroloquinoline quinone ameliorates diabetic cardiomyopathy by inhibiting the pyroptosis signaling pathway in C57BL/6 mice and AC16 cells.

Autor: Qu XF; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Zhai BZ; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Hu WL; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Lou MH; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Chen YH; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Liu YF; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Chen JG; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Mei S; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., You ZQ; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Liu Z; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Zhang LJ; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China., Zhang YH; Department of Basic Medical Science, Chongqing Three Gorges Medical College, Tianxing Road 366th, Chongqing, 404120, People's Republic of China. cqsxyzzyh@163.com., Wang Y; Institute of Food Science and Engineering, Hangzhou Medical College, Tianmushan Road 182th, Hangzhou, 310013, Zhejiang, People's Republic of China. wy3333@hmc.edu.cn.
Jazyk: angličtina
Zdroj: European journal of nutrition [Eur J Nutr] 2022 Jun; Vol. 61 (4), pp. 1823-1836. Date of Electronic Publication: 2022 Jan 08.
DOI: 10.1007/s00394-021-02768-w
Abstrakt: Purpose: Diabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism.
Methods: Diabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h.
Results: PQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy-(ANP and BNP), myocardial fibrosis-(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions.
Conclusion: PQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM. Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.
(© 2021. The Author(s).)
Databáze: MEDLINE
Nepřihlášeným uživatelům se plný text nezobrazuje