Journal
LIFE SCIENCES
Volume 256, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2020.117972
Keywords
Adenosine kinase; Ischemia-reperfusion; Acute kidney injury
Funding
- National Natural Science Foundation of China [81670628, 81870469, 81300573]
- Natural Science Foundation of Jiangsu Province [BK20131030]
- 333 Project of Jiangsu Province
- Six Talent Peaks Project in Jiangsu Province [WSN-010]
- China Scholarship Council (CSC) [201608320124]
- Chinese Society of Nephrology [17010060675]
- Clinic Research Center of Jiangsu Province [BL2014080]
- Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions
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Acute kidney injury (AKI) has a high morbidity and mortality, and there is no targeted treatment yet. One of the main causes of AKI is ischemia-reperfusion (IR). Increased release of adenosine under stress and hypoxia exerts anti-inflammatory and antioxidant effects. Adenosine kinase (ADK) is an important enzyme that eliminates adenosine in cells, and can maintain low adenosine concentration in cells. Our previous studies have shown that pretreatment of adenosine kinase inhibitor ABT-702 could markedly attenuate cisplatin-induced nephrotoxicity both in vivo and in vitro. This study is designed to investigate the effect of ADK inhibition on IR-induced AKI. The results showed that ADK expression was positively correlated with the degree of renal tubular injury, which suggested that the degree of ADK inhibition reflected the severity of acute tubular necrosis. In vivo, ADK inhibitor could reduce IR-induced renal injury, which might play a protective role by increasing tissue adenosine level, inhibiting oxidative stress, and reducing cell apoptosis. In HK2 cells, cobaltous dichloride (CoCl2) increased the level of oxidative stress, up-regulated the production of pro-inflammatory factor, and induced apoptosis, ADK inhibition could alleviate the above damaging effects. Moreover, the anti-apoptotic effect exerted by ADK inhibition was independent of inosine. In summary, our results support the idea that ADK inhibition has protective effects on IR-induced AKI. Adenosine kinase inhibition might provide a new target for AKI prevention and treatment.
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