Background: Adenosine provides renovascular protection in mouse models of ischemia-reperfusion injury (I/RI) through purinergic members of the G protein-coupled receptor family, such as the adenosine 2A receptor (A2AR). Ectonucleotidases CD39 and CD73 are integral vascular and immune nucleotidases that regulate extracellular adenosine signaling. Current investigation of CD39 and CD73 in renal I/RI has primarily focused on their respective roles in ischemic preconditioning.
Methods: In this study, we established a unilateral renal I/RI model and investigated the role of adenosine generation versus nucleotide removal in mediating protection in renal I/RI using mice deficient in CD39, CD73 or A2AR, thereby sequentially disrupting ectonucleotidase cascade and adenosinergic signaling.
Results: Compared with wild-type mice, Cd73 null mice showed reduced levels of serum creatinine and urea, apoptosis of renal cells, and histologic damage after I/RI. Deletion of CD39 was associated with severe renal injury. Administration of apyrase, a soluble form of CD39, decreased global apoptosis and I/RI induced renal injury in wild-type mice. Apyrase treatment also improved renal histology to some extent in A2AR null mice.
Conclusion: The relative protective effect of CD73 deletion in renal I/RI may reflect an effect of AMP accumulation. Deletion of CD39 showed deleterious effects and administration of soluble CD39 exerted renal protection, which is partially mediated by A2AR. The protective effect conferred by apyrase suggests that supplementing CD39 NTPDase activity may be a useful therapeutic strategy in renal transplantation.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1097/TP.0b013e31819022bc | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Remote limb ischemic pre-conditioning prevents renal Ischemia/reperfusion injury in rats by modulating oxidative stress and TNF-α/NF-κB/TGF-/βapelin signaling pathway.
Mol Biol Rep
November 2024
Nephro-Urology Research Center, Shiraz University of Medical Sciences, Research Tower, Khalili Avenue, Shiraz, 7193635899, Iran.
Background: Remote limb ischemic pre-conditioning (RIPreC) can invoke potent renal protection. The involvement of oxidative stress and inflammatory pathways in renal ischemia/reperfusion injury (I/RI) was also confirmed. This study was designed to investigate the RIPreC effects on IRI-induced kidney dysfunction in rats through NFĸB/TNF-α/TGF-ꞵ/apelin signaling pathway.
View Article and Find Full Text PDFArticle Synopsis
- The study investigates the protective effect of isoflurane preconditioning (IsoP) against kidney damage from ischemia/reperfusion injury (I/RI) in diabetic rats.
- Researchers compared various groups, including diabetic rats subjected to I/RI with and without IsoP, assessing kidney function, oxidative stress, inflammation, and cell apoptosis.
- Results show that IsoP significantly reduces kidney injury in diabetic conditions by enhancing the Brg1/Nrf2/HO-1 signaling pathway, indicating its potential as a therapeutic strategy for diabetic kidney injury.
Mitochondrial fumarate promotes ischemia/reperfusion-induced tubular injury.
Acta Physiol (Oxf)
April 2024
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Article Synopsis
- Mitochondrial dysfunction plays a key role in causing injury to tubular epithelial cells during renal ischemic/reperfusion injury (I/RI), although the specific mechanisms are not fully understood.
- Using advanced metabolic profiling techniques, the study found that tubular injury, which happens during the reperfusion phase, is linked to increased glycolysis and mitochondrial dysfunction.
- The research revealed that fumarate, produced from dysfunctional mitochondria and associated with a deficiency in fumarate hydratase, disrupts glutathione balance, leading to tubular injury, while targeting the signaling pathways can provide potential therapeutic benefits.
The combined effect of zinc oxide nanoparticles and milrinone on acute renal ischemia/reperfusion injury in rats: Potential underlying mechanisms.
Life Sci
June 2023
Department of Physiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt.
Aim: To investigate the efficacy of zinc oxide nanoparticles (ZnO-NPs) and/or milrinone (MIL) on renal ischemia/reperfusion injury (I/RI) in rats and their possible underlying mechanisms.
Materials And Methods: Forty-eight adult male Sprague-Dawley albino rats were randomly assigned into six equal-sized groups (n = 8): normal control, sham-operated, I/R group (45 min/24 h), ZnO-NPs group (10 mg/kg i.p.
Probenecid induces the recovery of renal ischemia/reperfusion injury via the blockade of Pannexin 1/P2X7 receptor axis.
Life Sci
November 2022
Electron Microscopy Department, Theodor Bilharz Research Institute, Warrak El-Hadar, Imbaba (P.O. 30), Giza 12411, Egypt.
Article Synopsis
- Renal ischemia/reperfusion injury (RI/RI) is a major cause of acute kidney injury, but effective treatments are lacking.
- Probenecid (PBN), a drug usually for gout, has shown protective effects in other types of injury and was tested for its impact on RI/RI in rats, resulting in reduced kidney damage and inflammation.
- The study highlights PBN’s ability to promote kidney recovery by inhibiting certain receptors and signaling pathways while enhancing regulatory T cells, suggesting it could be a promising treatment for kidney injuries.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!