Modulation of cellular redox homeostasis by the endocannabinoid system

Open Biology

Volumn 6, Issue 4, 2016, Pages

  Lipina, Christopher ^a   Hundal, Harinder S ^a  

^a UNIVERSITY OF DUNDEE   (United Kingdom)

Author keywords

Antioxidant; Cannabinoid receptor; Endocannabinoid system; Oxidative stress; Reactive oxygen species; Redox homeostasis

Indexed keywords

ENDOCANNABINOID; REACTIVE OXYGEN METABOLITE;

ANIMAL; BIOLOGICAL MODEL; HOMEOSTASIS; HUMAN; METABOLISM; OXIDATION REDUCTION REACTION; SIGNAL TRANSDUCTION;

ANIMALS; ENDOCANNABINOIDS; HOMEOSTASIS; HUMANS; MODELS, BIOLOGICAL; OXIDATION-REDUCTION; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION;

EID: 84987757856     PISSN: None     EISSN: 20462441     Source Type: Journal    
DOI: 10.1098/rsob.150276     Document Type: Article

References (126)

1. Griendling KK, Ushio-Fukai M. 2000 Reactive oxygen species as mediators of angiotensin II signaling. Regul. Pept 91, 21-27. (doi:10.1016/S0167-0115(00)00136-1)
2. Droge W. 2002 Free radicals in the physiological control of cell function. Physiol. Rev. 82, 47-95. (doi:10.1152/physrev.00018.2001)
3. Valencia A, Moran J. 2001 Role of oxidative stress in the apoptotic cell death of cultured cerebellar granule neurons. J. Neurosci. Res. 64, 284-297. (doi:10.1002/jnr.1077)
4. Ha JS, Lim HM, Park SS. 2010 Extracellular hydrogen peroxide contributes to oxidative glutamate toxicity. Brain Res. 1359, 291-297. (doi:10.1016/j.brainres. 2010.08.086)
5. Lu X, Xu H, Sun B, Zhu Z, Zheng D, Li X. 2013 Enhanced neuroprotective effects of resveratrol delivered by nanoparticles on hydrogen peroxideinduced oxidative stress in rat cortical cell culture. Mol. Pharm. 10, 2045-2053. (doi:10.1021/mp400056c)
6. Simonian NA, Coyle JT. 1996 Oxidative stress in neurodegenerative diseases. Annu. Rev. Pharmacol. Toxicol. 36, 83-106. (doi:10.1146/annurev.pa.36. 040196.000503)
7. Castilho RF, Ward MW, Nicholls DG. 1999 Oxidative stress, mitochondrial function, and acute glutamate excitotoxicity in cultured cerebellar granule cells. J. Neurochem. 72, 1394-1401. (doi:10.1046/j.1471-4159.1999.721394.x)
8. Markesbery WR, Carney JM. 1999 Oxidative alterations in Alzheimer's disease. Brain Pathol. 9, 133-146. (doi:10.1111/j.1750-3639.1999.tb00215.x)
9. Dhalla NS, Temsah RM, Netticadan T. 2000 Role of oxidative stress in cardiovascular diseases. J. Hypertens. 18, 655-673. (doi:10.1097/00004872-200018060-00002)
10. Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. 2007 Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44-84. (doi:10.1016/j. biocel.2006.07.001)
11. Zhao ZY, Luan P, Huang SX, Xiao SH, Zhao J, Zhang B, Gu BB, Pi RB, Liu J. 2013 Edaravone protects HT22 neurons from H2O2-induced apoptosis by inhibiting the MAPK signaling pathway. CNS Neurosci. Ther. 19, 163-169. (doi:10.1111/cns. 12044)
12. Massey V, Strickland S, Mayhew SG, Howell LG, Engel PC, Matthews RG, Schuman M, Sullivan PA. 1969 The production of superoxide anion radicals in the reaction of reduced flavins and flavoproteins with molecular oxygen. Biochem. Biophys. Res. Commun. 36, 891-897. (doi:10.1016/0006-291X(69)90287-3)
13. Heinzel B, John M, Klatt P, Bohme E, Mayer B. 1992 Ca2+/calmodulin-dependent formation of hydrogen peroxide by brain nitric oxide synthase. Biochem. J. 281, 627-630. (doi:10.1042/bj2810627)
14. Bokoch GM, Knaus UG. 2003 NADPH oxidases: not just for leukocytes anymore! Trends Biochem. Sci. 28, 502-508. (doi:10.1016/s0968-0004(03)00194-4)
15. Zangar RC, Davydov DR, Verma S. 2004 Mechanisms that regulate production of reactive oxygen species by cytochrome P450. Toxicol. Appl. Pharmacol. 199, 316-331. (doi:10.1016/j.taap.2004.01.018)
16. Klebanoff SJ. 2005 Myeloperoxidase: friend and foe. J. Leukoc. Biol. 77, 598-625. (doi:10.1189/jlb. 1204697)
17. Burdon RH. 1995 Superoxide and hydrogen peroxide in relation to mammalian cell proliferation. Free Radic. Biol. Med. 18, 775-794. (doi:10.1016/0891-5849(94)00198-S)
18. Behrend L, Henderson G, Zwacka RM. 2003 Reactive oxygen species in oncogenic transformation. Biochem. Soc. Trans. 31, 1441-1444. (doi:10.1042/bst0311441)
19. Paravicini TM, Touyz RM. 2006 Redox signaling in hypertension. Cardiovasc. Res. 71, 247-258. (doi:10.1016/j.cardiores.2006.05.001)
20. Bartosz G. 2009 Reactive oxygen species: destroyers or messengers? Biochem. Pharmacol. 77, 1303-1315. (doi:10.1016/j.bcp.2008.11.009)
21. McCord JM, Fridovich I. 1969 Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J. Biol. Chem. 244, 6049-6055.
22. Folz RJ, Crapo JD. 1994 Extracellular superoxide dismutase (SOD3): tissue-specific expression, genomic characterization, and computer-assisted sequence analysis of the human EC SOD gene. Genomics 22, 162-171. (doi:10.1006/geno.1994. 1357)
23. Yamamoto K, Volkl A, Hashimoto T, Fahimi HD. 1988 Catalase in guinea pig hepatocytes is localized in cytoplasm, nuclear matrix and peroxisomes. Eur. J. Cell Biol. 46, 129-135.
24. Oberley TD, Oberley LW, Slattery AF, Lauchner LJ, Elwell JH. 1990 Immunohistochemical localization of antioxidant enzymes in adult Syrian hamster tissues and during kidney development. Am. J. Pathol. 137, 199-214.
25. Brigelius-Flohe R, Maiorino M. 2013 Glutathione peroxidases. Biochim. Biophys. Acta 1830, 3289-3303. (doi:10.1016/j.bbagen.2012.11.020)
26. Paulsen CE, Carroll KS. 2010 Orchestrating redox signaling networks through regulatory cysteine switches. ACS Chem. Biol. 5, 47-62. (doi:10.1021/cb900258z)
27. Di Marzo V, Petrocellis LD. 2006 Plant, synthetic, and endogenous cannabinoids in medicine. Annu. Rev. Med. 57, 553-574. (doi:10.1146/annurev.med. 57.011205.135648)
28. Mukhopadhyay P et al. 2010 CB1 cannabinoid receptors promote oxidative stress and cell death in murine models of doxorubicin-induced cardiomyopathy and in human cardiomyocytes. Cardiovasc. Res. 85, 773-784. (doi:10.1093/cvr/cvp369)
29. Sugamura K et al. 2010 Cannabinoid 1 receptor blockade reduces atherosclerosis with enhances reverse cholesterol transport. J. Atheroscler. Thromb. 17, 141-147. (doi:10.5551/jat.2865)
30. Sun J, Fang Y, Chen T, Guo J, Yan J, Song S, Zhang L, Liao H. 2013 WIN55, 212-2 promotes differentiation of oligodendrocyte precursor cells and improve remyelination through regulation of the phosphorylation level of the ERK 1/2 via cannabinoid receptor 1 after stroke-induced demyelination. Brain Res. 1491, 225-235. (doi:10. 1016/j.brainres.2012.11.006)
31. Basavarajappa BS. 2007 Neuropharmacology of the endocannabinoid signaling system: molecular mechanisms, biological actions and synaptic plasticity. Curr. Neuropharmacol. 5, 81-97. (doi:10. 2174/157015907780866910)
32. Alger BE, Kim J. 2011 Supply and demand for endocannabinoids. Trends Neurosci. 34, 304-315. (doi:10.1016/j.tins.2011.03.003)
33. Okamoto Y, Morishita J, Tsuboi K, Tonai T, Ueda N. 2004 Molecular characterization of a phospholipase D generating anandamide and its congeners. J. Biol. Chem. 279, 5298-5305. (doi:10.1074/jbc. M306642200)
34. Ueda N, Tsuboi K, Uyama T, Ohnishi T. 2011 Biosynthesis and degradation of the endocannabinoid 2-arachidonoylglycerol. BioFactors (Oxford, England) 37, 1-7. (doi:10.1002/biof.131)
35. Taschler U et al. 2011 Monoglyceride lipase deficiency in mice impairs lipolysis and attenuates diet-induced insulin resistance. J. Biol. Chem. 286, 17 467-17 477. (doi:10.1074/jbc.M110.215434)
36. Devane WA, Dysarz FAIII, Johnson MR, Melvin LS, Howlett AC. 1988 Determination and characterization of a cannabinoid receptor in rat brain. Mol. Pharmacol. 34, 605-613.
37. Matsuda LA, Lolait SJ, Brownstein MJ, Young AC, Bonner TI. 1990 Structure of a cannabinoid receptor and functional expression of the cloned cDNA. Nature 346, 561-564. (doi:10.1038/346561a0)
38. Cencioni MT, Chiurchiu V, Catanzaro G, Borsellino G, Bernardi G, Battistini L, Maccarrone M. 2010 Anandamide suppresses proliferation and cytokine release from primary human T-lymphocytes mainly via CB2 receptors. PLoS ONE 5, e8688. (doi:10.1371/journal.pone.0008688)
39. Desroches J, Charron S, Bouchard JF, Beaulieu P. 2013 Endocannabinoids decrease neuropathic painrelated behavior in mice through the activation of one or both peripheral CB1 and CB2 receptors. Neuropharmacology 77, 441-452. (doi:10.1016/j. neuropharm.2013.10.006)
40. Lipina C, Stretton C, Hastings S, Hundal JS, Mackie K, Irving AJ, Hundal HS. 2010 Regulation of MAP kinase-directed mitogenic and protein kinase B-mediated signaling by cannabinoid receptor type 1 in skeletal muscle cells. Diabetes 59, 375-385. (doi:10.2337/db09-0979)
41. Tedesco L et al. 2010 Cannabinoid receptor stimulation impairs mitochondrial biogenesis in mouse white adipose tissue, muscle, and liver: the role of eNOS, p38 MAPK, and AMPK pathways. Diabetes 59, 2826-2836. (doi:10.2337/db09-1881)
42. Jbilo O et al. 2005 The CB1 receptor antagonist rimonabant reverses the diet-induced obesity phenotype through the regulation of lipolysis and energy balance. FASEB J. 19, 1567-1569. (doi:10. 1096/fj.04-3177fje)
43. Eckardt K et al. 2009 Cannabinoid type 1 receptors in human skeletal muscle cells participate in the negative crosstalk between fat and muscle. Diabetologia 52, 664-674. (doi:10.1007/s00125-008-1240-4)
44. Huang NL, Juang JM, Wang YH, Hsueh CH, Liang YJ, Lin JL, Tsai CT, Lai LP. 2010 Rimonabant inhibits TNF-a-induced endothelial IL-6 secretion via CB1 receptor and cAMP-dependent protein kinase pathway. Acta Pharmacol. Sin. 31, 1447-1453. (doi:10.1038/aps.2010.126)
45. Li Q, Wang F, Zhang YM, Zhou JJ, Zhang Y. 2013 Activation of cannabinoid type 2 receptor by JWH133 protects heart against ischemia/reperfusion-induced apoptosis. Cell Physiol. Biochem. 31, 693-702. (doi:10.1159/000350088)
46. Deveaux V et al. 2009 Cannabinoid CB2 receptor potentiates obesity-associated inflammation, insulin resistance and hepatic steatosis. PLoS ONE 4, e5844. (doi:10.1371/journal.pone.0005844)
47. South T, Huang XF. 2008 Temporal and site-specific brain alterations in CB1 receptor binding in high fat diet-induced obesity in C57Bl/6 mice. J. Neuroendocrinol. 20, 1288-1294. (doi:10.1111/j. 1365-2826.2008.01785.x)
48. Athanasiou A et al. 2007 Cannabinoid receptor agonists are mitochondrial inhibitors: a unified hypothesis of how cannabinoids modulate mitochondrial function and induce cell death. Biochem. Biophys. Res. Commun. 364, 131-137. (doi:10.1016/j.bbrc.2007.09.107)
49. Gustafsson K, Christensson B, Sander B, Flygare J. 2006 Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212-2 is associated with ceramide accumulation and p38 activation in mantle cell lymphoma. Mol. Pharmacol. 70, 1612-1620. (doi:10.1124/mol.106. 025981)
50. Mechoulam R et al. 1995 Identification of an endogenous 2-monoglyceride, present in canine gut, that binds to cannabinoid receptors. Biochem. Pharmacol. 50, 83-90. (doi:10.1016/0006-2952(95)00109-D)
51. O'Hare JD, Zielinski E, Cheng B, Scherer T, Buettner C. 2011 Central endocannabinoid signaling regulates hepatic glucose production and systemic lipolysis. Diabetes 60, 1055-1062. (doi:10.2337/db10-0962)
52. Bouaboula M, Poinot-Chazel C, Bourrie B, Canat X, Calandra B, Rinaldi-Carmona M, Le Fur G, Casellas P. 1995 Activation of mitogen-activated protein kinases by stimulation of the central cannabinoid receptor CB1. Biochem. J. 312, 637-641. (doi:10. 1042/bj3120637)
53. Landsman RS, Burkey TH, Consroe P, Roeske WR, Yamamura HI. 1997 SR141716A is an inverse agonist at the human cannabinoid CB1 receptor. Eur. J. Pharmacol. 334, R1-R2. (doi:10.1016/S0014-2999(97)01160-6)
54. O'Sullivan SE. 2007 Cannabinoids go nuclear: evidence for activation of peroxisome proliferatoractivated receptors. Br. J. Pharmacol. 152, 576-582. (doi:10.1038/sj.bjp.0707423)
55. Miyashita K, Oyama T, Sakuta T, Tokuda M, Torii M. 2012 Anandamide induces matrix metalloproteinase-2 production through cannabinoid-1 receptor and transient receptor potential vanilloid-1 in human dental pulp cells in culture. J. Endodont. 38, 786-790. (doi:10.1016/j. joen.2012.02.025)
56. Sharir H, Console-Bram L, Mundy C, Popoff SN, Kapur A, Abood ME. 2012 The endocannabinoids anandamide and virodhamine modulate the activity of the candidate cannabinoid receptor GPR55. J. Neuroimmune Pharmacol. 7, 856-865. (doi:10. 1007/s11481-012-9351-6)
57. Carracedo A, Geelen MJ, Diez M, Hanada K, Guzman M, Velasco G. 2004 Ceramide sensitizes astrocytes to oxidative stress: protective role of cannabinoids. Biochem. J. 380, 435-440. (doi:10.1042/bj20031714)
58. Mnich K, Finn DP, Dowd E, Gorman AM. 2010 Inhibition by anandamide of 6-hydroxydopamineinduced cell death in PC12 cells. Int. J. Cell Biol. 2010, 818497. (doi:10.1155/2010/818497)
59. Aso E, Juves S, Maldonado R, Ferrer I. 2013 CB2 cannabinoid receptor agonist ameliorates Alzheimer-like phenotype in AbetaPP/PS1 mice. J. Alzheimers Dis. 35, 847-858. (doi:10.3233/jad-130137)
60. Ribeiro R, Wen J, Li S, Zhang Y. 2013 Involvement of ERK1/2, cPLA2 and NF-kB in microglia suppression by cannabinoid receptor agonists and antagonists. Prostaglandins Other Lipid Mediat. 100-101, 1-14. (doi:10.1016/j.prostaglandins. 2012.11.003)
61. Kim SH, Won SJ, Mao XO, Jin K, Greenberg DA. 2005 Involvement of protein kinase A in cannabinoid receptor-mediated protection from oxidative neuronal injury. J. Pharmacol. Exp. Ther. 313, 88-94. (doi:10.1124/jpet.104.079509)
62. Goncharov I, Weiner L, Vogel Z. 2005 Delta9-tetrahydrocannabinol increases C6 glioma cell death produced by oxidative stress. Neuroscience 134, 567-574. (doi:10.1016/j.neuroscience.2005.04.042)
63. Mukhopadhyay P, Rajesh M, Pan H, Patel V, Mukhopadhyay B, Batkai S, Gao B, Hasko G, Pacher P. 2010 Cannabinoid-2 receptor limits inflammation, oxidative/nitrosative stress, and cell death in nephropathy. Free Radic. Biol. Med. 48, 457-467. (doi:10.1016/j.freeradbiomed.2009.11. 022)
64. Montecucco F, Lenglet S, Braunersreuther V, Burger F, Pelli G, Bertolotto M, Mach F, Steffens S. 2009 CB(2) cannabinoid receptor activation is cardioprotective in a mouse model of ischemia/reperfusion. J. Mol. Cell Cardiol. 46, 612-620. (doi:10.1016/j.yjmcc.2008.12.014)
65. Cao Z et al. 2013 Monoacylglycerol lipase controls endocannabinoid and eicosanoid signaling and hepatic injury in mice. Gastroenterology 144, 808-817.e15. (doi:10.1053/j.gastro.2012.12.028)
66. Batkai S et al. 2007 Cannabinoid-2 receptor mediates protection against hepatic ischemia/reperfusion injury. FASEB J. 21, 1788-1800. (doi:10.1096/fj.06-7451com)
67. Pacher P, Hasko G. 2008 Endocannabinoids and cannabinoid receptors in ischaemia-reperfusion injury and preconditioning. Br. J. Pharmacol. 153, 252-262. (doi:10.1038/sj.bjp.0707582)
68. Pacher P, Mechoulam R. 2011 Is lipid signaling through cannabinoid 2 receptors part of a protective system? Prog. Lipid Res. 50, 193-211. (doi:10. 1016/j.plipres.2011.01.001)
69. Han KH et al. 2009 CB1 and CB2 cannabinoid receptors differentially regulate the production of reactive oxygen species by macrophages. Cardiovasc. Res. 84, 378-386. (doi:10.1093/cvr/cvp240)
70. Rajesh M, Mukhopadhyay P, Hasko G, Liaudet L, Mackie K, Pacher P. 2010 Cannabinoid-1 receptor activation induces reactive oxygen speciesdependent and-independent mitogen-activated protein kinase activation and cell death in human coronary artery endothelial cells. Br. J. Pharmacol. 160, 688-700. (doi:10.1111/j.1476-5381.2010. 00712.x)
71. Costa MA, Fonseca BM, Keating E, Teixeira NA, Correia-da-Silva G. 2014 2-Arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells. Reproduction 147, 301-311. (doi:10.1530/rep-13-0563)
72. Jorgacevic B, Mladenovic D, Ninkovic M, Veskovic M, Dragutinovic V, Vatazevic A, Vucevic D, Jesic Vukicevic R, Radosavljevic T. 2015 Rimonabant improves oxidative/nitrosative stress in mice with nonalcoholic fatty liver disease. Oxid. Med. Cell Longev. 2015, 842108. (doi:10.1155/2015/842108)
73. Mukhopadhyay P et al. 2007 Pharmacological inhibition of CB1 cannabinoid receptor protects against doxorubicin-induced cardiotoxicity. J. Am. Coll. Cardiol. 50, 528-536. (doi:10.1016/j.jacc.2007. 03.057)
74. Rajesh M et al. 2012 Cannabinoid 1 receptor promotes cardiac dysfunction, oxidative stress, inflammation, and fibrosis in diabetic cardiomyopathy. Diabetes 61, 716-727. (doi:10. 2337/db11-0477)
75. Mukhopadhyay P et al. 2010 CB1 cannabinoid receptors promote oxidative/nitrosative stress, inflammation and cell death in a murine nephropathy model. Br. J. Pharmacol. 160, 657-668. (doi:10.1111/j.1476-5381.2010.00769.x)
76. Dando I, Donadelli M, Costanzo C, Dalla Pozza E, D'Alessandro A, Zolla L, Palmieri M. 2013 Cannabinoids inhibit energetic metabolism and induce AMPK-dependent autophagy in pancreatic cancer cells. Cell Death Dis. 4, e664. (doi:10.1038/ cddis.2013.151)
77. Sarfaraz S, Afaq F, Adhami VM, Mukhtar H. 2005 Cannabinoid receptor as a novel target for the treatment of prostate cancer. Cancer Res. 65, 1635-1641. (doi:10.1158/0008-5472.can-04-3410)
78. Qamri Z, Preet A, Nasser MW, Bass CE, Leone G, Barsky SH, Ganju RK. 2009 Synthetic cannabinoid receptor agonists inhibit tumor growth and metastasis of breast cancer. Mol. Cancer Ther. 8, 3117-3129. (doi:10.1158/1535-7163.mct-09-0448)
79. Donadelli M et al. 2011 Gemcitabine/cannabinoid combination triggers autophagy in pancreatic cancer cells through a ROS-mediated mechanism. Cell Death Dis. 2, e152. (doi:10.1038/cddis.2011.36)
80. Chen H et al. 2011 Oxidative stress in ischemic brain damage: mechanisms of cell death and potential molecular targets for neuroprotection. Antioxid. Redox Signal. 14, 1505-1517. (doi:10.1089/ars. 2010.3576)
81. Paramo B, Montiel T, Hernandez-Espinosa DR, Rivera-Martinez M, Moran J, Massieu L. 2013 Calpain activation induced by glucose deprivation is mediated by oxidative stress and contributes to neuronal damage. Int. J. Biochem. Cell Biol. 45, 2596-2604. (doi:10.1016/j.biocel.2013.08.013)
82. Jia J, Ma L, Wu M, Zhang L, Zhang X, Zhai Q, Jiang T, Wang Q, Xiong L. 2014 Anandamide protects HT22 cells exposed to hydrogen peroxide by inhibiting CB1 receptor-mediated type 2 NADPH oxidase. Oxid. Med. Cell Longev. 2014, 893516. (doi:10.1155/2014/893516)
83. Coskun ZM, Bolkent S. 2014 Oxidative stress and cannabinoid receptor expression in type-2 diabetic rat pancreas following treatment with Delta(9)-THC. Cell Biochem. Funct. 32, 612-619. (doi:10.1002/cbf. 3058)
84. Tiyerili V, Zimmer S, Jung S, Wassmann K, Naehle CP, Lutjohann D, Zimmer A, Nickenig G, Wassmann S. 2010 CB1 receptor inhibition leads to decreased vascular AT1 receptor expression, inhibition of oxidative stress and improved endothelial function. Basic Res. Cardiol. 105, 465-477. (doi:10.1007/ s00395-010-0090-7)
85. Zoppi S, Perez Nievas BG, Madrigal JL, Manzanares J, Leza JC, Garcia-Bueno B. 2011 Regulatory role of cannabinoid receptor 1 in stress-induced excitotoxicity and neuroinflammation. Neuropsychopharmacology 36, 805-818. (doi:10. 1038/npp.2010.214)
86. Kim J, Watkins BA. 2014 Cannabinoid receptor antagonists and fatty acids alter endocannabinoid system gene expression and COX activity. J. Nutr. Biochem. 25, 815-823. (doi:10.1016/j.jnutbio.2014. 03.012)
87. Zoppi S, Madrigal JL, Caso JR, Garcia-Gutierrez MS, Manzanares J, Leza JC, Garcia-Bueno B. 2014 Regulatory role of the cannabinoid CB2 receptor in stress-induced neuroinflammation in mice. Br. J. Pharmacol. 171, 2814-2826. (doi:10.1111/ bph.12607)
88. Velasco G, Galve-Roperh I, Sanchez C, Blazquez C, Haro A, Guzman M. 2005 Cannabinoids and ceramide: two lipids acting hand-by-hand. Life Sci. 77, 1723-1731. (doi:10.1016/j.lfs.2005.05. 015)
89. Cianchi F et al. 2008 Cannabinoid receptor activation induces apoptosis through tumor necrosis factor alpha-mediated ceramide de novo synthesis in colon cancer cells. Clin. Cancer Res. 14, 7691-7700. (doi:10.1158/1078-0432.ccr-08-0799)
90. Cinar R, Godlewski G, Liu J, Tam J, Jourdan T, Mukhopadhyay B, Harvey-White J, Kunos G. 2014 Hepatic cannabinoid-1 receptors mediate dietinduced insulin resistance by increasing de novo synthesis of long-chain ceramides. Hepatology 59, 143-153. (doi:10.1002/hep.26606)
91. Zhang DX, Zou AP, Li PL. 2003 Ceramide-induced activation of NADPH oxidase and endothelial dysfunction in small coronary arteries. Am. J. Physiol. Heart Circ. Physiol. 284, H605-H612. (doi:10.1152/ajpheart. 00697.2002)
92. Chen YY, Hsu MJ, Sheu JR, Lee LW, Hsieh CY. 2013 Andrographolide, a novel NF-kB inhibitor, induces vascular smooth muscle cell apoptosis via a ceramide-p47phox-ROS signaling cascade. Evid.-Based Complement. Alternat. Med. 2013, 821813. (doi:10.1155/2013/821813)
93. Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzman M, Brownlee M. 2001 Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J. Biol. Chem. 276, 25 096-25 100. (doi:10.1074/jbc.M007383200)
94. Van Herreweghe F, Mao J, Chaplen FW, Grooten J, Gevaert K, Vandekerckhove J, Vancompernolle K. 2002 Tumor necrosis factor-induced modulation of glyoxalase I activities through phosphorylation by PKA results in cell death and is accompanied by the formation of a specific methylglyoxal-derived AGE. Proc. Natl Acad. Sci. USA 99, 949-954. (doi:10. 1073/pnas.012432399)
95. El Jamali A, Freund C, Rechner C, Scheidereit C, Dietz R, Bergmann MW. 2004 Reoxygenation after severe hypoxia induces cardiomyocyte hypertrophy in vitro: activation of CREB downstream of GSK3b. FASEB J. 18, 1096-1098. (doi:10.1096/fj.03-1054fje)
96. Boissel JP, Bros M, Schrock A, Godtel-Armbrust U, Forstermann U. 2004 Cyclic AMP-mediated upregulation of the expression of neuronal NO synthase in human A673 neuroepithelioma cells results in a decrease in the level of bioactive NO production: analysis of the signaling mechanisms that are involved. Biochemistry 43, 7197-7206. (doi:10.1021/bi0302191)
97. Savchenko VL. 2013 Regulation of NADPH oxidase gene expression with PKA and cytokine IL-4 in neurons and microglia. Neurotox. Res. 23, 201-213. (doi:10.1007/s12640-012-9327-6)
98. Childers SR, Deadwyler SA. 1996 Role of cyclic AMP in the actions of cannabinoid receptors. Biochem. Pharmacol. 52, 819-827. (doi:10.1016/0006-2952(96)00419-4)
99. Asimaki O, Mangoura D. 2011 Cannabinoid receptor 1 induces a biphasic ERK activation via multiprotein signaling complex formation of proximal kinases PKCepsilon, Src, and Fyn in primary neurons. Neurochem. Int. 58, 135-144. (doi:10.1016/j. neuint.2010.11.002)
100. Wang W, Cao X, Liu C, Liu L. 2012 Cannabinoid WIN 55,212-2 inhibits TRPV1 in trigeminal ganglion neurons via PKA and PKC pathways. Neurol. Sci. 33, 79-85. (doi:10.1007/s10072-011-0620-6)
101. Ma L, Jia J, Liu X, Bai F, Wang Q, Xiong L. 2015 Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling. Biochem. Biophys. Res. Commun. 458, 92-97. (doi:10.1016/j.bbrc.2015.01.073)
102. Garcia DE, Brown S, Hille B, Mackie K. 1998 Protein kinase C disrupts cannabinoid actions by phosphorylation of the CB1 cannabinoid receptor. J. Neurosci. 18, 2834-2841.
103. Lv P et al. 2012 Phosphorylation of smooth muscle 22alpha facilitates angiotensin II-induced ROS production via activation of the PKCdelta-P47phox axis through release of PKCdelta and actin dynamics and is associated with hypertrophy and hyperplasia of vascular smooth muscle cells in vitro and in vivo. Circ. Res. 111, 697-707. (doi:10.1161/circresaha. 112.272013)
104. Chen F, Yu Y, Haigh S, Johnson J, Lucas R, Stepp DW, Fulton DJ. 2014 Regulation of NADPH oxidase 5 by protein kinase C isoforms. PLoS ONE 9, e88405. (doi:10.1371/journal.pone.0088405)
105. Pandey D, Fulton DJ. 2011 Molecular regulation of NADPH oxidase 5 via the MAPK pathway. Am. J. Physiol. Heart Circ. Physiol. 300, H1336-H1344. (doi:10.1152/ajpheart.01163.2010)
106. Ahn KH, Mahmoud MM, Kendall DA. 2012 Allosteric modulator ORG27569 induces CB1 cannabinoid receptor high affinity agonist binding state, receptor internalization, and Gi protein-independent ERK1/2 kinase activation. J. Biol. Chem. 287, 12 070-12082. (doi:10.1074/jbc.M111.316463)
107. Franklin JM, Carrasco GA. 2013 Cannabinoid receptor agonists upregulate and enhance serotonin 2A (5-HT2A) receptor activity via ERK1/2 signaling. Synapse 67, 145-159. (doi:10.1002/syn. 21626)
108. Vida M et al. 2014 CB1 blockade potentiates downregulation of lipogenic gene expression in perirenal adipose tissue in high carbohydrate diet-induced obesity. PLoS ONE 9, e90016. (doi:10.1371/journal. pone.0090016)
109. Tanaka Y, Gavrielides MV, Mitsuuchi Y, Fujii T, Kazanietz MG. 2003 Protein kinase C promotes apoptosis in LNCaP prostate cancer cells through activation of p38 MAPK and inhibition of the Akt survival pathway. J. Biol. Chem. 278, 33 753-33 762. (doi:10.1074/jbc.M303313200)
110. Wang Y et al. 2014 Effects of cannabinoid receptor type 2 on endogenous myocardial regeneration by activating cardiac progenitor cells in mouse infarcted heart. Sci. China Life Sci. 57, 201-208. (doi:10.1007/s11427-013-4604-z)
111. Nguyen T, Nioi P, Pickett CB. 2009 The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 284, 13 291-13 295. (doi:10.1074/jbc. R900010200)
112. Siegmund SV, Qian T, de Minicis S, Harvey-White J, Kunos G, Vinod KY, Hungund B, Schwabe RF. 2007 The endocannabinoid 2-arachidonoyl glycerol induces death of hepatic stellate cells via mitochondrial reactive oxygen species. FASEB J. 21, 2798-2806. (doi:10.1096/fj.06-7717com)
113. Ma L, Jia J, Niu W, Jiang T, Zhai Q, Yang L, Bai F, Wang Q, Xiong L. 2015 Mitochondrial CB1 receptor is involved in ACEA-induced protective effects on neurons and mitochondrial functions. Sci. Rep. 5, 12440. (doi:10.1038/srep12440)
114. Balenga NA et al. 2011 GPR55 regulates cannabinoid 2 receptor-mediated responses in human neutrophils. Cell Res. 21, 1452-1469. (doi:10.1038/cr.2011.60)
115. Ma F, Zhang L, Westlund KN. 2009 Reactive oxygen species mediate TNFR1 increase after TRPV1 activation in mouse DRG neurons. Mol. Pain 5, 31. (doi:10.1186/1744-8069-5-31)
116. Chavez AE, Chiu CQ, Castillo PE. 2010 TRPV1 activation by endogenous anandamide triggers postsynaptic long-term depression in dentate gyrus. Nat. Neurosci. 13, 1511-1518. (doi:10.1038/nn. 2684)
117. Talbot S, Dias JP, Lahjouji K, Bogo MR, Campos MM, Gaudreau P, Couture R. 2012 Activation of TRPV1 by capsaicin induces functional kinin B(1) receptor in rat spinal cord microglia. J. Neuroinflammation 9, 16. (doi:10.1186/1742-2094-9-16)
118. Hofmann NA, Barth S, Waldeck-Weiermair M, Klec C, Strunk D, Malli R, Graier WF. 2014 TRPV1 mediates cellular uptake of anandamide and thus promotes endothelial cell proliferation and networkformation. Biol. Open 3, 1164-1172. (doi:10.1242/ bio.20149571)
119. Adam-Vizi V, Starkov AA. 2010 Calcium and mitochondrial reactive oxygen species generation: how to read the facts. J. Alzheimers Dis. 20(Suppl. 2), S413-S426. (doi:10.3233/jad-2010-100465)
120. Pandey D, Gratton JP, Rafikov R, Black SM, Fulton DJ. 2011 Calcium/calmodulin-dependent kinase II mediates the phosphorylation and activation of NADPH oxidase 5. Mol. Pharmacol. 80, 407-415. (doi:10.1124/mol.110.070193)
121. Nishio S et al. 2012 Activation of CaMKII as a key regulator of reactive oxygen species production in diabetic rat heart. J. Mol. Cell Cardiol. 52, 1103-1111. (doi:10.1016/j.yjmcc.2012.02.006)
122. Toyama T, Nakamura H, Harano Y, Yamauchi N, Morita A, Kirishima T, Minami M, Itoh Y, Okanoue T. 2004 PPARalpha ligands activate antioxidant enzymes and suppress hepatic fibrosis in rats. Biochem. Biophys. Res. Commun. 324, 697-704. (doi:10.1016/j.bbrc.2004.09.110)
123. Chung SS et al. 2009 Glutathione peroxidase 3 mediates the antioxidant effect of peroxisome proliferator-activated receptor gamma in human skeletal muscle cells. Mol. Cell Biol. 29, 20-30. (doi:10.1128/mcb.00544-08)
124. Marsicano G, Moosmann B, Hermann H, Lutz B, Behl C. 2002 Neuroprotective properties of cannabinoids against oxidative stress: role of the cannabinoid receptor CB1. J. Neurochem. 80, 448-456. (doi:10.1046/j.0022-3042.2001.00716.x)
125. Wang M, Abais JM, Meng N, Zhang Y, Ritter JK, Li PL, Tang WX. 2014 Upregulation of cannabinoid receptor-1 and fibrotic activation of mouse hepatic stellate cells during Schistosoma J. infection: role of NADPH oxidase. Free Radic. Biol. Med. 71, 109-120. (doi:10.1016/j.freeradbiomed.2014.03.015)
126. Wei Y, Wang X, Wang L. 2009 Presence and regulation of cannabinoid receptors in human retinal pigment epithelial cells. Mol. Vis. 15, 1243-1251.