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Calcium/calmodulin-dependent protein kinase Ⅱ regulates adriamycin induced renal tubular epithelial cell apoptosis in mice with acute renal injury via Yes associated protein

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Author:
No author available
Journal Title:
Chinese Journal of Biomedical Engineering
Issue:
5
DOI:
10.3760/cma.j.cn115668-20211115-00139
Key Word:
钙/钙调素依赖性蛋白激酶Ⅱ;Yes相关蛋白;急性肾损伤;多柔比星;细胞凋亡;Calcium/calmodulin dependent protein kinase Ⅱ;Yes associated protein;Acute renal injury;Doxorubicin;Apoptosis

Abstract: Objective:To investigate whether calcium/calmodulin dependent protein kinase Ⅱ (CaMK Ⅱ) and Yes-associated protein (YAP) are involved in apoptosis of renal tubular epithelial cells (RTEC) in acute renal injury (AKI) and the underlying mechanisms.Methods:Fifteen female BALB/c mice aged 6-8 weeks were randomly divided into the normal control group, adriamycin (ADR) intervention group and ADR + CaMK Ⅱ inhibitor (K) intervention group ( n=5 each) . AKI was modeled in mice by ADR intervention. HE staining was used to observe the renal tubular cell injury. Enzyme-linked immunosorbent assay was used to measure the serum creatinine level in the mice. The RTEC apoptosis model was established in vitro by ADR intervention of HK-2 cells. Flow cytometry was used to examine the effects of ADR, ADR+K, YAP siRNA, CaMK Ⅱ activator (C) , and C + YAP overexpression (oYAP) on the apoptosis rates. Western blotting was used to measure the expression of total Bax and Bcl-2 proteins, cytoplasmic (pCaMK Ⅱ) and total proteins of CaMK Ⅱ, and nuclear YAP protein in mouse renal tissues and the HK-2 cells. Results:Compared with the normal control group, ADR intervention increased the RTEC injury and serum creatinine level in mice, and the RTEC injury and the serum creatinine level were lowered after administration of K (all P<0.05) . The ADR intervention group had significantly higher rate of RTEC apoptosis than that in the control group ( P<0.05) , and the apoptosis was attenuated after administration of K ( P<0.05) . Compared with the normal control group and the siRNA blank control group, the apoptosis rate of RTEC treated with YAP siRNA and C was significantly increased (both P<0.05) . The apoptosis rate of C-treated RTEC was reduced in the presence of oYAP ( P<0.05) . Compared with the normal control group, the RTEC and mouse renal tissue cells intervened by ADR showed higher protein expression of pCaMK Ⅱ/CaMK Ⅱ and Bax, and lower protein expression of nuclear YAP and total Bcl-2 (all P<0.05) . These effects were alleviated after administration of K (all P<0.05) . Conclusion:CaMK Ⅱ may regulate ADR-induced apoptosis of RTEC in AKI mice via YAP.

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