TRPA1 as a promising target in ischemia/reperfusion: A comprehensive review

Document Type : Review Article

Authors

1 Cardio-Oncology Research Center, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

2 Department of Echocardiography, Rajaie Cardiovascular Medical and Research Center, Iran University of Medical Sciences, Tehran, Iran

3 Pharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran

4 4 Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran

5 Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran

Abstract

Ischemic disorders, including myocardial infarction, cerebral ischemia, and peripheral vascular impairment, are the main common reasons for debilitating diseases and death in Western cultures. Ischemia occurs when blood circulation is reduced in tissues. Reperfusion, although commanded to return oxygen to ischemic tissues, generates paradoxical tissue responses. The responses include generating reactive oxygen species (ROS), stimulating inflammatory responses in ischemic organs, endoplasmic reticulum stress, and the expansion of postischemic capillary no-reflow, which intensifies organ damage. Multiple pathologic processes contribute to ischemia/reperfusion; therefore, targeting different pathologic processes may yield an effective therapeutic approach. Transient Receptor Potential A1 (TRPA1) belongs to the TRP family of ion channels, detects a broad range of chemicals, and promotes the transduction of noxious stimuli, e.g., methylglyoxal, ROS, and acrolein effects are attributed to the channel’s sensitivity to intracellular calcium elevation or phosphoinositol phosphate modulation. Hypoxia and ischemia are associated with oxidative stress, which activates the TRPA1 channel. This review describes the role of TRPA1 and its related mechanisms that contribute to ischemia/reperfusion. Relevant articles were searched from PubMed, Scopus, Web of Sciences, and Google Scholar electronic databases, up to the end of August 2023. Based on the evidence presented here, TRPA1 may have protective or deteriorative functions during the ischemia/reperfusion process. Its function depends on the activation level, the ischemic region, the extent of lesions, and the duration of ischemia.

Keywords

Main Subjects


1. Akbari G, Ali Mard S, Veisi A. A comprehensive review on regulatory effects of crocin on ischemia/reperfusion injury in multiple organs. Biomed Pharmacother 2018; 99:664-670.
2. Makhdoumi P, Roohbakhsh A, Karimi G. MicroRNAs regulate mitochondrial apoptotic pathway in myocardial ischemia-reperfusion-injury. Biomed Pharmacother 2016; 84:1635-1644.
3. Minutoli L, Puzzolo D, Rinaldi M, Irrera N, Marini H, Arcoraci V, et al. ROS-mediated NLRP3 inflammasome activation in brain, heart, kidney, and testis ischemia/reperfusion injury. Oxid Med Cell Longev 2016; 2016:2183026.
4. Kalogeris T, Baines CP, Krenz M, Korthuis RJ. Ischemia/reperfusion. Compr Physiol 2016; 7:113-170.
5. Maida CD, Norrito RL, Daidone M, Tuttolomondo A, Pinto A. Neuroinflammatory mechanisms in ischemic stroke: Focus on cardioembolic stroke, background, and therapeutic approaches. Int J Mol Sci 2020; 21:6454-6486.
6. Soler EP, Ruiz VC. Epidemiology and risk factors of cerebral ischemia and ischemic heart diseases: similarities and differences. Curr Cardiol Rev 2010; 6:138-149.
7. Vishwakarma VK, Upadhyay PK, Gupta JK, Yadav HN. Pathophysiologic role of ischemia reperfusion injury: A review. J Indian Coll Cardiol 2017; 7:97-104.
8. Alavi MS, Shamsizadeh A, Karimi G, Roohbakhsh A. Transient receptor potential ankyrin 1 (TRPA1)-mediated toxicity: friend or foe? Toxicol Mech Methods 2020; 30:1-18.
9. Talavera K, Startek JB, Alvarez-Collazo J, Boonen B, Alpizar YA, Sanchez A, et al. Mammalian transient receptor potential TRPA1 channels: From structure to disease. Physiol Rev 2020; 100:725-803.
10. Wu Y, Chen AW, Goodnough CL, Lu Y, Zhang Y, Gross ER. IcyHot analgesic topical cream limits cardiac injury in rodents. Transl Res 2021; 227:42-52.
11. Takahashi N, Kuwaki T, Kiyonaka S, Numata T, Kozai D, Mizuno Y, et al. TRPA1 underlies a sensing mechanism for O2. Nat Chem Biol 2011; 7:701-711.
12. Etemad L, Karimi G, Alavi MS, Roohbakhsh A. Pharmacological effects of cannabidiol by transient receptor potential channels. Life Sci 2022; 300:120582.
13. Takahashi N, Chen HY, Harris IS, Stover DG, Selfors LM, Bronson RT, et al. Cancer cells co-opt the neuronal redox-sensing channel TRPA1 to promote oxidative-stress tolerance. Cancer Cell 2018; 33:985-1003.e1007.
14. Paulsen CE, Armache JP, Gao Y, Cheng Y, Julius D. Structure of the TRPA1 ion channel suggests regulatory mechanisms. Nature 2015; 520:511-517.
15. Trevisani M, Siemens J, Materazzi S, Bautista DM, Nassini R, Campi B, et al. 4-Hydroxynonenal, an endogenous aldehyde, causes pain and neurogenic inflammation through activation of the irritant receptor TRPA1. Proc Natl Acad Sci U S A 2007; 104:13519-13524.
16. Wang Z, Ye D, Ye J, Wang M, Liu J, Jiang H, et al. The TRPA1 channel in the cardiovascular system: Promising features and challenges. Front Pharmacol 2019; 10:1253.
17. Bugger H, Pfeil K. Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochim Biophys Acta Mol Basis Dis
2020;1866:165768.
18. Wu L, Xiong X, Wu X, Ye Y, Jian Z, Zhi Z, et al. Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Front Mol Neurosci 2020; 13:28-40.
19. Kim S, Hwang SW. Emerging roles of TRPA1 in sensation of oxidative stress and its implications in defense and danger. Arch Pharm Res 2013; 36:783-791.
20. Lu Y, Piplani H, McAllister SL, Hurt CM, Gross ER. Transient receptor potential ankyrin 1 activation within the cardiac myocyte limits ischemia-reperfusion injury in rodents. Anesthesiology 2016; 125:1171-1180.
21. Li S, Sun X, Wu H, Yu P, Wang X, Jiang Z, et al. TRPA1 promotes cardiac myofibroblast transdifferentiation after myocardial infarction injury via the calcineurin-NFAT-DYRK1A signaling pathway. Oxid Med Cell Longev 2019; 2019:6408352.
22. Li R, Liu R, Yan F, Zhuang X, Shi H, Gao X. Inhibition of TRPA1 promotes cardiac repair in mice after myocardial infarction. J Cardiovasc Pharmacol 2020; 75:240-249.
23. Lin L, Wang X, Yu Z. Ischemia-reperfusion injury in the brain: mechanisms and potential therapeutic strategies. Biochem Pharmacol (Los Angel). 2016; 5:213.
24. Jurcau A, Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: from pathophysiology to therapeutic strategies. Int J Mol Sci 2021; 23:14.
25. Pires PW, Earley S. Neuroprotective effects of TRPA1 channels in the cerebral endothelium following ischemic stroke. Elife 2018; 7:e35316.
26. Zaki OS, Nassar NN, Abdallah DM, Safar MM, Mohammed RA. Cilostazol alleviates NLRP3 inflammasome-induced allodynia/hyperalgesia in murine cerebral cortex following transient ischemia: Focus on TRPA1/glutamate and Akt/dopamine/BDNF/Nrf2 trajectories. Mol Neurobiol 2022; 59:7194-7211.
27. Hamilton NB, Kolodziejczyk K, Kougioumtzidou E, Attwell D. Proton-gated Ca2+-permeable TRP channels damage myelin in conditions mimicking ischaemia. Nature 2016; 529:523-527.
28. Giacco V, Flower G, Artamonova M, Hunter J, Padilla Requerey A, Hamilton NB. Transient receptor potential Ankyrin‐1 (TRPA1) agonists suppress myelination and induce demyelination in organotypic cortical slices. Glia 2023; 71:1402-1413.
29. Lajoso W, Flower G, Giacco V, Kaul A, La Mache C, Brăban A, et al. Transient receptor potential ankyrin-1 (TRPA1) block protects against loss of white matter function during ischaemia in the mouse optic nerve. Pharmaceuticals (Basel) 2021; 14:909-920.
30. Zhou T, Li J, Cheng A, Zuo Z. Desflurane post-treatment reduces hypoxic-ischemic brain injury via reducing transient receptor potential ankyrin 1 in neonatal rats. Neuroscience 2023; 522:121-131.
31. Hoebart C, Kiss A, Pilz PM, Szabo PL, Podesser BK, Fischer MJM, et al. TRPA1 as target in myocardial infarction. Int J Mol Sci 2023; 24:2516.
32. Ahmadian Salami A, Alavi MS, Souri MS, Roohbakhsh A. Involvement of the transient receptor potential A1 in morphine-induced conditioned place preference and physical dependence in mice. Can J Physiol Pharmacol 2022; 100:1135-1142.
33. Andrei SR, Ghosh M, Sinharoy P, Damron DS. Stimulation of TRPA1 attenuates ischemia-induced cardiomyocyte cell death through an eNOS-mediated mechanism. Channels (Austin) 2019; 13:192-206.
34. Ma Y, Iyer RP, Jung M, Czubryt MP, Lindsey ML. Cardiac fibroblast activation post-myocardial infarction: current knowledge gaps. Trends Pharmacol Sci 2017; 38:448-458.
35. Conklin DJ, Guo Y, Nystoriak MA, Jagatheesan G, Obal D, Kilfoil PJ, et al. TRPA1 channel contributes to myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol 2019; 316:H889-H899.
36. Üstünel L, Özgüler IM. The effects of iloprost and beta3 receptor agonist on TRPA1 and TRPC1 immunreactivity in an experimental lower extremty ischemia-reperfusion injury model. Turk J Med Sci 2021; 51:2763-2770.
37. Ma S, Wang DH. Knockout of Trpa1 exacerbates renal ischemia-reperfusion injury with classical activation of macrophages. Am J Hypertens 2021; 34:110-116.
38. So K, Tei Y, Zhao M, Miyake T, Hiyama H, Shirakawa H, et al. Hypoxia-induced sensitisation of TRPA1 in painful dysesthesia evoked by transient hindlimb ischemia/reperfusion in mice. Sci Rep 2016; 6:23261.
39. Klafke JZ, da Silva MA, Rossato MF, de Prá SD, Rigo FK, Walker CI, et al. Acute and chronic nociceptive phases observed in a rat hind paw ischemia/reperfusion model depend on different mechanisms. Pflugers Arch 2016; 468:229-241.
40. De Logu F, De Prá SD, de David Antoniazzi CT, Kudsi SQ, Ferro PR, Landini L, et al. Macrophages and Schwann cell TRPA1 mediate chronic allodynia in a mouse model of complex regional pain syndrome type I. Brain Behav Immun 2020; 88:535-546.
41. Baek S-S, Kim S-H. Treadmill exercise ameliorates symptoms of Alzheimer disease through suppressing microglial activation-induced apoptosis in rats. J Exerc Rehabil 2016; 12:526.
42. Sasaki A, Mizoguchi S, Kagaya K, Shiro M, Sakai A, Andoh T, et al. A mouse model of peripheral postischemic dysesthesia: involvement of reperfusion-induced oxidative stress and TRPA1 channel. J Pharmacol Exp Ther 2014; 351:568-575.
43. Hiyama H, Yano Y, So K, Imai S, Nagayasu K, Shirakawa H, et al. TRPA1 sensitization during diabetic vascular impairment contributes to cold hypersensitivity in a mouse model of painful diabetic peripheral neuropathy. Mol Pain 2018; 14:1744806918789812.
44. Xing J, Lu J, Li J. TRPA1 mediates amplified sympathetic responsiveness to activation of metabolically sensitive muscle afferents in rats with femoral artery occlusion. Front Physiol 2015; 6:249.
45. Xing J, Li J. TRPA1 function in skeletal muscle sensory neurons following femoral artery occlusion. Cell Physiol Biochem 2017; 42:2307-2317.
46. Xing J, Li J. Proteinase-activated receptor-2 sensitivity of amplified TRPA1 activity in skeletal muscle afferent nerves and exercise pressor reflex in rats with femoral artery occlusion. Cell Physiol Biochem 2017; 44:163-171.
47. Pizzimenti S, Ciamporcero ES, Daga M, Pettazzoni P, Arcaro A, Cetrangolo G, et al. Interaction of aldehydes derived from lipid peroxidation and membrane proteins. Front Physiol 2013; 4:242.
48. Lin Y, Chen Z, Tang J, Cao P, Shi R. Acrolein contributes to the neuropathic pain and neuron damage after ischemic-reperfusion spinal cord injury. Neuroscience 2018; 384:120-130.
49. Qin Q, Yu N, Gu Y, Ke W, Zhang Q, Liu X, et al. Inhibiting multiple forms of cell death optimizes ganglion cells survival after retinal ischemia reperfusion injury. Cell Death & Disease 2022; 13:507.
50. Souza Monteiro de Araújo D, De Logu F, Adembri C, Rizzo S, Janal MN, Landini L, et al. TRPA1 mediates damage of the retina induced by ischemia and reperfusion in mice. Cell Death Dis 2020; 11:633.
51. Araújo DSM, Miya-Coreixas VS, Pandolfo P, Calaza KC. Cannabinoid receptors and TRPA1 on neuroprotection in a model of retinal ischemia. Exp Eye Res 2017; 154:116-125.
52. Malek M, Nematbakhsh M. Renal ischemia/reperfusion injury; from pathophysiology to treatment. J Renal Inj Prev 2015; 4:20-27.
53. Wu CK, Wu CL, Lee TS, Kou YR, Tarng DC. Renal tubular epithelial TRPA1 acts as an oxidative stress sensor to mediate ischemia-reperfusion-induced kidney injury through MAPKs/NF-κB signaling. Int J Mol Sci 2021; 22.
54. Den Hengst WA, Gielis JF, Lin JY, Van Schil PE, De Windt LJ, Moens AL. Lung ischemia-reperfusion injury: a molecular and clinical view on a complex pathophysiological process. Am J Physiol Heart Circ Physiol  2010; 299:H1283-H1299.
55. Taylor-Clark TE, Undem BJ. Sensing pulmonary oxidative stress by lung vagal afferents. Respir Physiol Neurobiol 2011; 178:406-413.
56. Gu X, Yu N, Pang X, Zhang W, Zhang J, Zhang Y. EXPRESS: Products of oxidative stress and TRPA1 expression in the brainstem of rats after lung ischemia-reperfusion injury. Pulm Circ 2019; 9:2045894019865169.
57. Zhang XH, Qi HX, Xu DS, Pang XC, Wang CY, Yu WJ. Expression of proteinase-activated receptor-2 and transient receptor potential A1 in vagal afferent nerve of rat after lung schemia-reperfusion injury. J Biol FRegul Homeost Agents 2019; 33:1405-1413.
58. Balestrini A, Joseph V, Dourado M, Reese RM, Shields SD, Rougé L, et al. A TRPA1 inhibitor suppresses neurogenic inflammation and airway contraction for asthma treatment. J Exp Med 2021; 218.
59. Hakimizadeh E, Shamsizadeh A, Roohbakhsh A, Arababadi MK, Hajizadeh MR, Shariati M, et al. TRPV1 receptor-mediated expression of Toll-like receptors 2 and 4 following permanent middle cerebral artery occlusion in rats. Iran J Basic Med Sci 2017; 20:863-869.