The MC4 receptor agonist RO27-3225 inhibits NLRP1-dependent neuronal pyroptosis via the ASK1/JNK/p38 MAPK pathway in a mouse model of intracerebral haemorrhage

British Journal of Pharmacology
Shengpan ChenJiping Tang

Abstract

Inflammasome-mediated pyroptosis is an important neuronal cell death mechanism. Previous studies reported that activation of melanocortin MC4 receptor exerted neuroprotection in several neurological diseases. Here, we have investigated the role of MC4 receptor activation with RO27-3225 in suppressing neuronal pyroptosis after experimental intracerebral haemorrhage (ICH) and the underlying mechanism. One hundred and sixty-nine male CD1 mice were used. ICH was induced by injection of bacterial collagenase into the right-side basal ganglia. RO27-3225, a selective agonist of MC4 receptor, was injected intraperitoneally at 1 hr after ICH. To elucidate the underlying mechanism, we used the specific MC4 receptor antagonist HS024 and NQDI-1, a specific inhibitor of the apoptosis signalling-regulating kinase 1 (ASK1). Neurological tests, Western blot, Fluoro-Jade C, TUNEL, and immunofluorescence staining were conducted. Expression of MC4 receptor and the NOD-like receptor family, pyrin domain containing 1 (NLRP1) inflammasome in brain were increased after ICH. RO27-3225 treatment decreased neuronal pyroptosis and neurobehavioural deficits at 24 and 72 hr after ICH. RO27-3225 reduced the expression of p-ASK1, p-JNK, p-p38 MAPK, NLRP1 inf...Continue Reading

References

Jul 31, 2001·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·S K JoN H Won
Jan 18, 2006·Neuropeptides·Sa Forslin AronssonMarianne Schultzberg
Jun 14, 2008·Trends in Neurosciences·Anna Catania
Dec 11, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Denise P AbulafiaW Dalton Dietrich
Apr 30, 2009·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Juan Pablo de Rivero VaccariRobert W Keane
Jun 23, 2009·Trends in Endocrinology and Metabolism : TEM·Alastair S GarfieldLora K Heisler
Jul 24, 2010·British Journal of Pharmacology·Carol KilkennyUNKNOWN NC3Rs Reporting Guidelines Working Group
Nov 3, 2010·British Journal of Pharmacology·Alessandra BittoFrancesco Squadrito
Jun 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ying CaiWon-Ki Kim
Nov 1, 2011·Critical Care Medicine·Alessandra BittoDomenica Altavilla
Jul 12, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Satoshi TomuraW Dalton Dietrich
Jan 11, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yang ShenNancy Y Ip
Oct 10, 2013·Ageing Research Reviews·David Yang-Wei FannThiruma V Arumugam
Dec 3, 2013·Progress in Neurobiology·Yu ZhouQing-Wu Yang
May 9, 2014·Experimental Neurology·David Yang-Wei FannThiruma V Arumugam
Dec 17, 2014·Cellular and Molecular Life Sciences : CMLS·Adriana R RodriguesAlexandra M Gouveia
Jan 16, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Saskia M BurmJeffrey J Bajramovic
Apr 17, 2015·Immunological Reviews·Joseph Chavarría-Smith, Russell E Vance
Jul 9, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Lu-Sha TongJohn H Zhang
Nov 20, 2016·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Anatol ManaenkoJiping Tang
Aug 22, 2017·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Budbazar EnkhjargalJohn H Zhang
Sep 28, 2017·Neuropharmacology·D Andrew WilkinsonGuohua Xi
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators
Oct 22, 2017·British Journal of Pharmacology·Stephen Ph AlexanderUNKNOWN CGTP Collaborators

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Citations

Apr 23, 2020·Frontiers in Cellular Neuroscience·Yuanjian FangJianmin Zhang
Jan 13, 2021·Pharmaceuticals·Roshan Dinparastisaleh, Mehdi Mirsaeidi
May 5, 2021·Journal of Physiology and Biochemistry·Xue GouYunman Li
Mar 13, 2021·Cell Biology International·Cai TanXiao-Gang Wan
Jul 5, 2021·Phytomedicine : International Journal of Phytotherapy and Phytopharmacology·Peng ZengQing Tian

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