8-Br-cADPR, a TRPM2 ion channel antagonist, inhibits renal ischemia-reperfusion injury.
Ersen EraslanAyhan TanyeliElif PolatElif PolatPublished in: Journal of cellular physiology (2018)
The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na+ and Ca 2+ . The TRPM2 ion channel is expressed in the kidney and can be activated by various molecules such as hydrogen peroxide, calcium, and cyclic adenosine diphosphate (ADP)-ribose (cADPR) that are produced during acute kidney injury. In this study, we investigated the role of 8-bromo-cyclic ADP-ribose (8-Br-cADPR; a cADPR antagonist) in renal ischemia-reperfusion injury using biochemical and histopathological parameters. CD38, cADPR, tumor necrosis factor-α, interleukin-1β, and myeloperoxidase (inflammatory markers), urea and creatinine, hydrogen peroxide (oxidant), and catalase (antioxidant enzyme) levels that increase with ischemia-reperfusion injury decreased in the groups treated with 8-Br-cADPR. In addition, renin levels were elevated in the groups treated with 8-Br-cADPR. Histopathological examination revealed that 8-Br-cADPR reduced renal damage and the expression of caspase-3 and TRPM2. Our results suggest that the inhibition of TRPM2 ion channel may be a new treatment modality for ischemic acute kidney injury.
Keyphrases
- hydrogen peroxide
- ischemia reperfusion injury
- oxidative stress
- acute kidney injury
- nitric oxide
- cell death
- rheumatoid arthritis
- cerebral ischemia
- cardiac surgery
- induced apoptosis
- risk assessment
- binding protein
- human health
- single cell
- transcription factor
- signaling pathway
- climate change
- high resolution
- atomic force microscopy