Abstract: TH-PO117
The Effect of Adenosine Kinase on Acute Renal Injury
Session Information
- AKI: Inflammation, New Technologies, Omics
October 25, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Acute Kidney Injury
- 103 AKI: Mechanisms
Authors
- Xing, Chang Ying, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Cao, Wei, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Yuan, Yanggang, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Zhang, Bo, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
- Mao, Huijuan, First Affiliated Hospital of Nanjing Medical University, Nanjing, JIangSu, China
Background
Numerous studies have demonstrated that several mechanisms, including necrosis, apoptosis, inflammatory reaction and oxidative stress are closely linked to acute kidney injury.Adenosine, emerging as a key regulatory molecule, is mostly protective in the pathophysiology of inflammatory diseases. Previous study showed that some of the adenosine receptors led to renal-protection against ischemia-reperfusion injury. However, these adenosine receptors agonists lack a useful therapeutic index due to cardiovascular side effects. We hypothesized that inhibition of adenosine kinase exacerbates extracellular adenosine levels to reduce cisplatin and ischemia reperfusion-induced renal injury.
Methods
1.(1)C57BL/6 mice(24g, 6-8week, male) were randomly divided into 4 groups: Control, ABT-702, Cisplatin, and ABT-702+ Cisplatin, (2)C57BL/6 mice were randomly divided into 4 groups: sham operation group (Sham), ABT-702,ischemia-reperfusion (IR), ABT-702 +IR group (ABT-702+IR),kidney pathological changes, and protective effects were observed.
2.(1) HK-2 cells were pretreated with 1uM ABT-702 then incubated with cisplatin at 20uM concentration for 24 h. (2) HK-2 cells were treated with the ADK small interfered RNA, then incubated with Cocl2 at 250uM concentration for 12 h to induce chemical hypoxia, followed by reperfusion for 24 h. The apoptosis-associated protein (cleaved caspase-3, Bcl-2, Bax), ROS, and four types of adenosine receptors were detected. Four receptors antagonists were added before ABT-702 to detect the changes in cell viability.
Results
In this study, inhibition of adenosine kinase could markedly attenuate cisplatin-induced and renal ischemia reperfusion-induced acute kidney injury, tubular cell apoptosis, oxidative stress and inflammation in the kidneys. Consistent to in vivo results, the inhibition of ADK suppressed cisplatin and Cocl2-induced apoptosis, ROS production and inflammation in HK2 cell. Additionally, the protective effect of ADK inhibition was abolished byA1 or A2Badenosine receptors inhibition and enhanced by A2Aor A3 adenosine receptors inhibitor.
Conclusion
Inhibition of ADK increases adenosine and attenuates acute renal injury by anti-inflammatory, antioxidant stress and anti-apoptosis mechanism and partly dependents on A1 and A2b receptors to protect HK2 cells injury.
Funding
- Government Support - Non-U.S.