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Bradykinin protects cardiac c‐kit positive cells from high‐glucose‐induced senescence through B2 receptor signaling pathway
Author(s) -
Fu Cong,
Cao Yuhan,
Li Bing,
Xu Rongfeng,
Sun Yuning,
Yao Yuyu
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29039
Subject(s) - bradykinin , senescence , receptor , chemistry , b2 receptor , microbiology and biotechnology , endocrinology , medicine , biology , biochemistry
Cardiac c‐kit positive cells are cardiac‐derived cells that exist within the heart and have a great many protective effects. The senescence of cardiac c‐kit positive cells probably leads to cell dysfunction. Bradykinin plays a key role in cell protection. However, whether bradykinin prevents cardiac c‐kit positive cells from high‐glucose‐induced senescence is unknown. Here, we found that glucose treatment causes the premature senescence of cardiac c‐kit positive cells. Bradykinin B2 receptor (B2R) expression was declined by glucose‐induced senescence. Bradykinin treatment inhibited senescence and reduced intracellular oxygen radicals according to senescence‐associated β‐galactosidase staining and 2′,7′‐dichlorodihydrofluorescein diacetate staining. Moreover, the mitochondrial membrane potential was damaged, as measured by JC‐1 staining. The mitochondrial membrane potential was preserved under bradykinin treatment. The concentration of superoxide was decreased, and the concentration of intracellular adenosine triphosphate was increased after bradykinin treatment. Western blot showed that bradykinin leads to AKT and mammalian target of rapamycin (mTOR) phosphorylation and decreased levels of P53 and P16 when compared with glucose treatment alone. Antagonists of B2R, phosphoinositide 3‐kinase (PI3K), mTOR, and B2R small interfering RNA prevented the protective effect of bradykinin. P53 antagonist also inhibited the glucose‐induced senescence of cardiac c‐kit positive cells. In conclusion, bradykinin prevents the glucose‐induced premature senescence of cardiac c‐kit positive cells through the B2R/PI3K/AKT/mTOR/P53 signal pathways.