Protective effect of N ‐( p ‐amylcinnamoyl) anthranilic acid, phospholipase A 2 enzyme inhibitor, and transient receptor potential melastatin‐2 channel blocker against renal ischemia–reperfusion injury

2018 ◽  
Vol 120 (3) ◽  
pp. 3822-3832 ◽  
Author(s):  
Murat Çakır ◽  
Suat Tekin ◽  
Aslı Taşlıdere ◽  
Pınar Çakan ◽  
Halil Düzova ◽  
...  
Keyword(s):  
Protective Effect ◽  
Transient Receptor Potential ◽  
Channel Blocker ◽  
Ischemia Reperfusion Injury ◽  
Enzyme Inhibitor ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Transient Receptor Potential Melastatin ◽  
Renal Ischemia Reperfusion Injury ◽  
Transient Receptor

scholarly journals Transient Receptor Potential Melastatin 2 Negatively Regulates LPS-ATP-Induced Caspase-1-Dependent Pyroptosis of Bone Marrow-Derived Macrophage by Modulating ROS Production

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Haihong Wang ◽  
Xinyi Zhou ◽  
Hui Li ◽  
Xiaowei Qian ◽  
Yan Wang ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Morphological Characteristics ◽  
Receptor Potential ◽  
Ros Production ◽  
Caspase 1 ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

Background. Pyroptosis, a new form of cell death, which has special morphological characteristics, depends on caspase-1 activation and occupies an important role in inflammatory immune diseases and ischemia-reperfusion injury. ROS is a common activator of NLR/caspase-1. Transient receptor potential melastatin 2 (TRPM2), a selective cation channel, is involved in inflammatory regulation. This study was designed to explore the role of TRPM2 in activating caspase-1 and caspase-1-dependent pyroptosis of mouse BMDMs. Methods. BMDMs isolated from WT and TRPM2−/− mice were treated with LPS and ATP, along with ROS inhibitor (NAC and DPI), caspase-1 inhibitor (Z-YVAD), or not. The activation of caspase-1 was measured by western blot. EtBr and EthD-2 staining were used to assess the incidence of pyroptosis. Results. Compared with WT, the activated caspase-1-P10 was higher and the percentage of EtBr positive cells was also increased in TRPM2−/− group, which were both inhibited by Z-YVAD, NAC, or DPI. ASC oligomerization was increased in TRPM2−/− group. Conclusion. Deletion of TRPM2 can enhance the activation of caspase-1 and pyroptosis, which may be via modulating ROS production, suggesting that TRPM2 plays a critical role in immune adjustment.

scholarly journals The second member of transient receptor potential-melastatin channel family protects hearts from ischemia-reperfusion injury

2013 ◽  
Vol 304 (7) ◽  
pp. H1010-H1022 ◽  
Author(s):  
Barbara A. Miller ◽  
JuFang Wang ◽  
Iwona Hirschler-Laszkiewicz ◽  
Erhe Gao ◽  
Jianliang Song ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Receptor Potential ◽  
Left Ventricular ◽  
Transient Receptor Potential Melastatin ◽  
Trpm2 Channels ◽  
Transient Receptor ◽  
Fractional Shortening

The second member of the transient receptor potential-melastatin channel family (TRPM2) is expressed in the heart and vasculature. TRPM2 channels were expressed in the sarcolemma and transverse tubules of adult left ventricular (LV) myocytes. Cardiac TRPM2 channels were functional since activation with H2O2 resulted in Ca2+ influx that was dependent on extracellular Ca2+, was significantly higher in wild-type (WT) myocytes compared with TRPM2 knockout (KO) myocytes, and inhibited by clotrimazole in WT myocytes. At rest, there were no differences in LV mass, heart rate, fractional shortening, and +dP/d t between WT and KO hearts. At 2–3 days after ischemia-reperfusion (I/R), despite similar areas at risk and infarct sizes, KO hearts had lower fractional shortening and +dP/d t compared with WT hearts. Compared with WT I/R myocytes, expression of the Na+/Ca2+ exchanger (NCX1) and NCX1 current were increased, expression of the α1-subunit of Na+-K+-ATPase and Na+ pump current were decreased, and action potential duration was prolonged in KO I/R myocytes. Post-I/R, intracellular Ca2+ concentration transients and contraction amplitudes were equally depressed in WT and KO myocytes. After 2 h of hypoxia followed by 30 min of reoxygenation, levels of ROS were significantly higher in KO compared with WT LV myocytes. Compared with WT I/R hearts, oxygen radical scavenging enzymes (SODs) and their upstream regulators (forkhead box transcription factors and hypoxia-inducible factor) were lower, whereas NADPH oxidase was higher, in KO I/R hearts. We conclude that TRPM2 channels protected hearts from I/R injury by decreasing generation and enhancing scavenging of ROS, thereby reducing I/R-induced oxidative stress.

scholarly journals Products of oxidative stress and transient receptor potential ankyrin A1 expression in the brainstem after lung ischemia–reperfusion injury

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986516 ◽  
Author(s):  
Xiaoying Gu ◽  
Yu Nan ◽  
Xiaochuan Pang ◽  
Wenwen Zhang ◽  
Jian Zhang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Receptor Potential ◽  
Antioxidant Response ◽  
Solitary Tract ◽  
Transient Receptor Potential A1 ◽  
Transient Receptor

Lung ischemia–reperfusion injury is a common clinical concern. As the injury occurs, the pulmonary afferent nerves play a key role in regulating respiratory functions under pathophysiological conditions. The present study was to examine products of oxidative stress and expression of transient receptor potential A1 in the commissural nucleus of the solitary tract after lung ischemia–reperfusion injury; and further to determine molecular mediators linking to activation of oxidative stress and transient receptor potential ankyrin A1. A rat model of lung ischemia–reperfusion injury was used. Enzyme-linked immunosorbent assay and western blot analysis were employed to examine products of oxidative stress (i.e. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine), and expression of transient receptor potential A1, Nrf2-antioxidant response element, and NADPH oxidase. 8-isoprostaglandin F2α and 8-hydroxy-2′-deoxyguanosine were amplified in the commissural nucleus of the solitary tract of lung ischemia–reperfusion injury rats, accompanied with downregulation of Nrf2-antioxidant response element, and upregulation of NOX4 and transient receptor potential A1. Blocking NADPH oxidase (subtype NOX4) decreased products of oxidative stress in the commissural nucleus of the solitary tract and attenuated upregulation of transient receptor potential A1 induced by lung ischemia–reperfusion injury. Our data revealed specific signaling pathways by which lung ischemia–reperfusion injury impairs Nrf2-antioxidant response and activates oxidative stress in the brainstem thereby leading to amplification of transient receptor potential A1 receptor likely via products of oxidative stress. Data suggest the abnormalities in the pulmonary afferent signals at the brainstem level which is likely to affect respiratory functions as lung ischemia–reperfusion injury occurs.

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