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Effect of cholestasis and NeuroAid treatment on the expression of Bax, Bcl-2, Pgc-1α and Tfam genes involved in apoptosis and mitochondrial biogenesis in the striatum of male rats

  • Mohammad NasehiEmail author
  • Sepehr Torabinejad
  • Mehrdad Hashemi
  • Salar Vaseghi
  • Mohammad-Reza Zarrindast
Original Article

Abstract

Cholestasis means impaired bile synthesis or secretion. In fact, it is a bile flow reduction following Bile Duct Ligation (BDL). Cholestasis has a main role in necrosis and apoptosis. Apoptosis is a form of programmed cell death that has intrinsic and extrinsic pathways. The intrinsic pathway is mediated by Bcl-2 (B cell lymphoma-2) proteins which integrate death and survival signals. Bcl-2 has anti-apoptotic and Bax has pro-apoptotic effects. Also, striatum is one of the brain regions that has high expressions of Bcl-2 proteins. Moreover, Tfam and Pgc-1α are involved in mitochondrial biogenesis. On the other hand, NeuroAid, is a drug that has neuroprotective and anti-apoptosis effects. In this study, using quantitative PCR, we measured the expression of all these genes in the striatum of male rats following BDL and NeuroAid administration. Results showed, BDL increased the expression of Bax and Tfam and decreased the expression of Bcl-2. NeuroAid restored the effect of BDL on the expression of Bax, while did not alter the effect of BDL on Bcl-2. In addition, it increased the expression of Tfam that was previously elevated by BDL and raised the expression of Tfam in normal rats. Both BDL and NeuroAid, had no effect on Pgc-1α. In conclusion, cholestasis increased the expression of Bax and decreased the expression of Bcl-2, and this effect may have related to enhanced susceptibility of mitochondrial pathways following oxidative stress. Tfam expression was increased following cholestasis and this effect may have related to cellular compensatory mechanisms against high accumulation of free radicals or mitochondrial biogenesis failure. Furthermore, NeuroAid may play a role against apoptosis and can be used to increase mitochondrial biogenesis.

Keywords

Cholestasis Bcl-2 Bax Tfam Pgc-1α NeuroAid 

Notes

Funding information

There is no providing financial support to this project.

Compliance with ethical standards

The study was carried out in accordance with ethical standards in all aspects.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. Aktas C, Kanter M, Erboga M, Mete R, Oran M (2014) Melatonin attenuates oxidative stress, liver damage and hepatocyte apoptosis after bile-duct ligation in rats. Toxicol Ind Health 30:835–844.  https://doi.org/10.1177/0748233712464811 CrossRefPubMedGoogle Scholar
  2. Arduini A et al (2011) Mitochondrial biogenesis fails in secondary biliary cirrhosis in rats leading to mitochondrial DNA depletion and deletions. Am J Physiol Gastrointest Liver Physiol 301:G119–G127.  https://doi.org/10.1152/ajpgi.00253.2010 CrossRefPubMedGoogle Scholar
  3. Assimakopoulos SF et al (2008) Superoxide radical formation in diverse organs of rats with experimentally induced obstructive jaundice. Redox Rep 13:179–184.  https://doi.org/10.1179/135100008X308902 CrossRefPubMedGoogle Scholar
  4. Balaban RS (2009) Domestication of the cardiac mitochondrion for energy conversion. J Mol Cell Cardiol 46:832–841.  https://doi.org/10.1016/j.yjmcc.2009.02.018 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Bouitbir J et al (2012) Opposite effects of statins on mitochondria of cardiac and skeletal muscles: a ‘mitohormesis’ mechanism involving reactive oxygen species and PGC-1. Eur Heart J 33:1397–1407.  https://doi.org/10.1093/eurheartj/ehr224 CrossRefPubMedGoogle Scholar
  6. Campbell CT, Kolesar JE, Kaufman BA (2012) Mitochondrial transcription factor A regulates mitochondrial transcription initiation, DNA packaging, and genome copy number. Biochim Biophys Acta 1819:921–929.  https://doi.org/10.1016/j.bbagrm.2012.03.002 CrossRefPubMedGoogle Scholar
  7. Chroni E, Patsoukis N, Karageorgos N, Konstantinou D, Georgiou C (2006) Brain oxidative stress induced by obstructive jaundice in rats. J Neuropathol Exp Neurol 65:193–198.  https://doi.org/10.1097/01.jnen.0000200152.98259.4e CrossRefPubMedGoogle Scholar
  8. Cong H, Du N, Yang Y, Song L, Zhang W, Tien P (2016) Enterovirus 71 2B induces cell apoptosis by directly inducing the conformational activation of the proapoptotic protein Bax. J Virol 90:9862–9877.  https://doi.org/10.1128/JVI.01499-16 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Coskun P, Wyrembak J, Schriner SE, Chen HW, Marciniack C, Laferla F, Wallace DC (2012) A mitochondrial etiology of Alzheimer and Parkinson disease. Biochim Biophys Acta 1820:553–564.  https://doi.org/10.1016/j.bbagen.2011.08.008 CrossRefPubMedGoogle Scholar
  10. de Andrade DC, de Carvalho SN, Pinheiro D, Thole AA, Moura AS, de Carvalho L, Cortez EA (2015) Bone marrow mononuclear cell transplantation improves mitochondrial bioenergetics in the liver of cholestatic rats. Exp Cell Res 336:15–22.  https://doi.org/10.1016/j.yexcr.2015.05.002 CrossRefPubMedGoogle Scholar
  11. Elmore S (2007) Apoptosis: a review of programmed cell death. Toxicol Pathol 35:495–516.  https://doi.org/10.1080/01926230701320337 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Friberg H, Wieloch T, Castilho RF (2002) Mitochondrial oxidative stress after global brain ischemia in rats. Neurosci Lett 334:111–114CrossRefGoogle Scholar
  13. Fudge JL, Haber SN (2002) Defining the caudal ventral striatum in primates: cellular and histochemical features. J Neurosci 22:10078–10082CrossRefGoogle Scholar
  14. Ghonem NS, Assis DN, Boyer JL (2015) Fibrates and cholestasis. Hepatology 62:635–643.  https://doi.org/10.1002/hep.27744 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Giam M, Huang DC, Bouillet P (2008) BH3-only proteins and their roles in programmed cell. Death Oncogene 27(Suppl 1):S128–S136.  https://doi.org/10.1038/onc.2009.50 CrossRefGoogle Scholar
  16. Good CH et al (2011) Impaired nigrostriatal function precedes behavioral deficits in a genetic mitochondrial model of Parkinson's disease. FASEB J 25:1333–1344.  https://doi.org/10.1096/fj.10-173625 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Green DR, Kroemer G (2004) The pathophysiology of mitochondrial cell death. Science 305:626–629.  https://doi.org/10.1126/science.1099320 CrossRefPubMedGoogle Scholar
  18. Guicciardi ME, Gores GJ (2009) Life and death by death receptors. FASEB J 23:1625–1637.  https://doi.org/10.1096/fj.08-111005 CrossRefPubMedPubMedCentralGoogle Scholar
  19. Han SY, Hong ZY, Xie YH, Zhao Y, Xu X (2017) Therapeutic effect of Chinese herbal medicines for post stroke recovery: a traditional and network meta-analysis. Medicine (Baltimore) 96:e8830.  https://doi.org/10.1097/MD.0000000000008830 CrossRefGoogle Scholar
  20. Han X, Cong H (2017) Enterovirus 71 induces apoptosis by directly modulating the conformational activation of pro-apoptotic protein Bax. J Gen Virol 98:422–434.  https://doi.org/10.1099/jgv.0.000705 CrossRefPubMedGoogle Scholar
  21. Hartmann A et al (2002) Increased expression and redistribution of the antiapoptotic molecule Bcl-xL in Parkinson's disease. Neurobiol Dis 10:28–32CrossRefGoogle Scholar
  22. Hemann MT, Lowe SW (2006) The p53-BCL-2 connection. Cell Death Differ 13:1256–1259.  https://doi.org/10.1038/sj.cdd.4401962 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Hetz C (2010) BCL-2 protein family. Essential regulators of cell death. Preface Adv Exp Med Biol 687:vii–viiiGoogle Scholar
  24. Heurteaux C et al (2010) Neuroprotective and neuroproliferative activities of NeuroAid (MLC601, MLC901), a Chinese medicine, in vitro and in vivo. Neuropharmacology 58:987–1001.  https://doi.org/10.1016/j.neuropharm.2010.01.001 CrossRefPubMedGoogle Scholar
  25. Hockenbery DM, Oltvai ZN, Yin XM, Milliman CL, Korsmeyer SJ (1993) BCL-2 functions in an antioxidant pathway to prevent apoptosis. Cell 75:241–251CrossRefGoogle Scholar
  26. Huang LT, Tiao MM, Tain YL, Chen CC, Hsieh CS (2009) Melatonin ameliorates bile duct ligation-induced systemic oxidative stress and spatial memory deficits in developing rats. Pediatr Res 65:176–180.  https://doi.org/10.1203/PDR.0b013e31818d5bc7 CrossRefPubMedGoogle Scholar
  27. Huang LT, Chen CC, Sheen JM, Chen YJ, Hsieh CS, Tain YL (2010) The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine. Int J Dev Neurosci 28:169–174.  https://doi.org/10.1016/j.ijdevneu.2009.11.006 CrossRefPubMedGoogle Scholar
  28. Igney FH, Krammer PH (2002) Death and anti-death: tumour resistance to apoptosis. Nat Rev Cancer 2:277–288.  https://doi.org/10.1038/nrc776 CrossRefPubMedGoogle Scholar
  29. Jagani H, Kasinathan N, Meka SR, Josyula VR (2016) Antiapoptotic BCL-2 protein as a potential target for cancer therapy: a mini review. Artif Cells Nanomed Biotechnol 44:1212–1221.  https://doi.org/10.3109/21691401.2015.1019668 CrossRefPubMedGoogle Scholar
  30. Javadi-Paydar M, Ghiassy B, Ebadian S, Rahimi N, Norouzi A, Dehpour AR (2013) Nitric oxide mediates the beneficial effect of chronic naltrexone on cholestasis-induced memory impairment in male rats. Behav Pharmacol 24:195–206.  https://doi.org/10.1097/FBP.0b013e3283618a8c CrossRefPubMedGoogle Scholar
  31. Kang D, Kim SH, Hamasaki N (2007) Mitochondrial transcription factor A (TFAM): roles in maintenance of mtDNA and cellular functions. Mitochondrion 7:39–44.  https://doi.org/10.1016/j.mito.2006.11.017 CrossRefPubMedGoogle Scholar
  32. Karavias DD et al (2003) BCL-2 and BAX expression and cell proliferation, after partial hepatectomy with and without ischemia, on cholestatic liver in rats: an experimental study. J Surg Res 110:399–408CrossRefGoogle Scholar
  33. Kloek JJ et al (2012) Cholestasis is associated with hepatic microvascular dysfunction and aberrant energy metabolism before and during ischemia-reperfusion. Antioxid Redox Signal 17:1109–1123.  https://doi.org/10.1089/ars.2011.4291 CrossRefPubMedGoogle Scholar
  34. Kohlhaas M et al (2010) Elevated cytosolic Na+ increases mitochondrial formation of reactive oxygen species in failing cardiac myocytes. Circulation 121:1606–1613.  https://doi.org/10.1161/CIRCULATIONAHA.109.914911 CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kunkel GH, Chaturvedi P, Thelian N, Nair R, Tyagi SC (2018) Mechanisms of TFAM-mediated cardiomyocyte protection. Can J Physiol Pharmacol 96:173–181.  https://doi.org/10.1139/cjpp-2016-0718 CrossRefPubMedGoogle Scholar
  36. Lee HC, Wei YH (2005) Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol 37:822–834.  https://doi.org/10.1016/j.biocel.2004.09.010 CrossRefPubMedGoogle Scholar
  37. Li H et al (2019) Relations of neuropeptide Y and heme oxygenase-1 expressions with fetal brain injury in rats with intrahepatic cholestasis of pregnancy. Acta Cir Bras 34:e201900401.  https://doi.org/10.1590/s0102-865020190040000001 CrossRefPubMedPubMedCentralGoogle Scholar
  38. Li R, Guo W, Fu Z, Ding G, Zou Y, Wang Z (2011) Hepatoprotective action of Radix Paeoniae Rubra aqueous extract against CCl4-induced hepatic damage. Molecules 16:8684–8694.  https://doi.org/10.3390/molecules16108684 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Li T, Apte U (2015) Bile acid metabolism and signaling in cholestasis, inflammation, and Cancer. Adv Pharmacol 74:263–302.  https://doi.org/10.1016/bs.apha.2015.04.003 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Ljubuncic P, Tanne Z, Bomzon A (2000) Evidence of a systemic phenomenon for oxidative stress in cholestatic liver disease. Gut 47:710–716.  https://doi.org/10.1136/gut.47.5.710 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Lleo A, Marzorati S, Anaya JM, Gershwin ME (2017) Primary biliary cholangitis: a comprehensive overview. Hepatol Int 11:485–499.  https://doi.org/10.1007/s12072-017-9830-1 CrossRefPubMedGoogle Scholar
  42. Lomonosova E, Chinnadurai G (2008) BH3-only proteins in apoptosis and beyond: an overview. Oncogene 27(Suppl 1):S2–S19 doi: https://doi.org/10.1038/onc.2009.39 CrossRefGoogle Scholar
  43. Magen I, Avraham Y, Ackerman Z, Vorobiev L, Mechoulam R, Berry EM (2009) Cannabidiol ameliorates cognitive and motor impairments in mice with bile duct ligation. J Hepatol 51:528–534.  https://doi.org/10.1016/j.jhep.2009.04.021 CrossRefPubMedGoogle Scholar
  44. Martinvalet D, Zhu P, Lieberman J (2005) Granzyme a induces caspase-independent mitochondrial damage, a required first step for apoptosis. Immunity 22:355–370.  https://doi.org/10.1016/j.immuni.2005.02.004 CrossRefPubMedGoogle Scholar
  45. Modo M et al (2017) Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease. PLoS One 12:e0180733.  https://doi.org/10.1371/journal.pone.0180733 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Moore GJ, Bebchuk JM, Wilds IB, Chen G, Manji HK (2000) Lithium-induced increase in human brain grey matter. Lancet 356:1241–1242CrossRefGoogle Scholar
  47. Nagatsu T (2002) Parkinson's disease: changes in apoptosis-related factors suggesting possible gene therapy. J Neural Transm (Vienna) 109:731–745.  https://doi.org/10.1007/s007020200061 CrossRefGoogle Scholar
  48. Nasehi M, Mohammadi A, Ebrahimi-Ghiri M, Hashemi M, Zarrindast MR (2019) MLC901 during sleep deprivation rescues fear memory disruption in rats. Naunyn Schmiedeberg’s Arch Pharmacol 392:813–821.  https://doi.org/10.1007/s00210-018-01612-z CrossRefGoogle Scholar
  49. Newman LA, Scavuzzo CJ, Gold PE, Korol DL (2017) Training-induced elevations in extracellular lactate in hippocampus and striatum: dissociations by cognitive strategy and type of reward. Neurobiol Learn Mem 137:142–153.  https://doi.org/10.1016/j.nlm.2016.12.001 CrossRefPubMedGoogle Scholar
  50. Nishiyama S et al (2010) Over-expression of Tfam improves the mitochondrial disease phenotypes in a mouse model system. Biochem Biophys Res Commun 401:26–31.  https://doi.org/10.1016/j.bbrc.2010.08.143 CrossRefPubMedGoogle Scholar
  51. Nisoli E, Clementi E, Moncada S, Carruba MO (2004) Mitochondrial biogenesis as a cellular signaling framework. Biochem Pharmacol 67:1–15CrossRefGoogle Scholar
  52. Oh SH, Yun KJ, Nan JX, Sohn DH, Lee BH (2003) Changes in expression and immunolocalization of protein associated with toxic bile salts-induced apoptosis in rat hepatocytes. Arch Toxicol 77:110–115.  https://doi.org/10.1007/s00204-002-0415-x CrossRefPubMedGoogle Scholar
  53. Parisi MA, Clayton DA (1991) Similarity of human mitochondrial transcription factor 1 to high mobility group proteins. Science 252:965–969CrossRefGoogle Scholar
  54. Parola M, Leonarduzzi G, Robino G, Albano E, Poli G, Dianzani MU (1996) On the role of lipid peroxidation in the pathogenesis of liver damage induced by long-standing cholestasis. Free Radic Biol Med 20:351–359CrossRefGoogle Scholar
  55. Peng K et al (2017) The interaction of mitochondrial biogenesis and fission/fusion mediated by PGC-1alpha regulates rotenone-induced dopaminergic neurotoxicity. Mol Neurobiol 54:3783–3797.  https://doi.org/10.1007/s12035-016-9944-9 CrossRefPubMedGoogle Scholar
  56. Perez MJ, Macias RI, Marin JJ (2006) Maternal cholestasis induces placental oxidative stress and apoptosis. Prot Eff Ursodeoxycholic Acid Placenta 27:34–41.  https://doi.org/10.1016/j.placenta.2004.10.020 CrossRefGoogle Scholar
  57. Pistritto G, Trisciuoglio D, Ceci C, Garufi A, D’Orazi G (2016) Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY) 8:603–619.  https://doi.org/10.18632/aging.100934 CrossRefGoogle Scholar
  58. Puigserver P, Spiegelman BM (2003) Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 24:78–90.  https://doi.org/10.1210/er.2002-0012 CrossRefPubMedGoogle Scholar
  59. Quintard H et al (2011) MLC901, a traditional Chinese medicine protects the brain against global ischemia. Neuropharmacology 61:622–631.  https://doi.org/10.1016/j.neuropharm.2011.05.003 CrossRefPubMedGoogle Scholar
  60. Rasouri S, Lagouge M, Auwerx J (2007) SIRT1/PGC-1: a neuroprotective axis? Med Sci (Paris) 23:840–844.  https://doi.org/10.1051/medsci/20072310840 CrossRefGoogle Scholar
  61. Renault TT, Chipuk JE (2014) Death upon a kiss: mitochondrial outer membrane composition and organelle communication govern sensitivity to BAK/BAX-dependent apoptosis. Chem Biol 21:114–123.  https://doi.org/10.1016/j.chembiol.2013.10.009 CrossRefPubMedGoogle Scholar
  62. Reza Zarrindast M, Eslimi Esfahani D, Oryan S, Nasehi M, Torabi Nami M (2013) Effects of dopamine receptor agonist and antagonists on cholestasis-induced anxiolytic-like behaviors in rats. Eur J Pharmacol 702:25–31.  https://doi.org/10.1016/j.ejphar.2013.01.023 CrossRefPubMedGoogle Scholar
  63. Rivera-Mancia S, Montes S, Mendez-Armenta M, Muriel P, Rios C (2009) Morphological changes of rat astrocytes induced by liver damage but not by manganese chloride exposure. Metab Brain Dis 24:243–255.  https://doi.org/10.1007/s11011-009-9138-5 CrossRefPubMedGoogle Scholar
  64. Schafer ZT et al (2009) Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature 461:109–113.  https://doi.org/10.1038/nature08268 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Serviddio G et al (2004) Ursodeoxycholic acid protects against secondary biliary cirrhosis in rats by preventing mitochondrial oxidative stress. Hepatology 39:711–720.  https://doi.org/10.1002/hep.20101 CrossRefPubMedGoogle Scholar
  66. Sheen JM, Chen YC, Tain YL, Huang LT (2014) Increased circulatory asymmetric dimethylarginine and multiple organ failure: bile duct ligation in rat as a model. Int J Mol Sci 15:3989–4006.  https://doi.org/10.3390/ijms15033989 CrossRefPubMedPubMedCentralGoogle Scholar
  67. Shi DY, Xie FZ, Zhai C, Stern JS, Liu Y, Liu SL (2009) The role of cellular oxidative stress in regulating glycolysis energy metabolism in hepatoma cells. Mol Cancer 8:32.  https://doi.org/10.1186/1476-4598-8-32 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Shipovskaya AA, Dudanova OP (2018) Intrahepatic cholestasis in nonalcoholic fatty liver disease. Ter Arkh 90:69–74.  https://doi.org/10.26442/terarkh201890269-74
  69. Singh L et al (2015) Expression of pro-apoptotic Bax and anti-apoptotic BCL-2 proteins in human retinoblastoma. Clin Exp Ophthalmol 43:259–267.  https://doi.org/10.1111/ceo.12397 CrossRefPubMedGoogle Scholar
  70. Singh S, Dikshit M (2007) Apoptotic neuronal death in Parkinson’s disease: involvement of nitric oxide. Brain Res Rev 54:233–250.  https://doi.org/10.1016/j.brainresrev.2007.02.001 CrossRefPubMedGoogle Scholar
  71. Sokol RJ, Devereaux M, Khandwala R, O'Brien K (1993) Evidence for involvement of oxygen free radicals in bile acid toxicity to isolated rat hepatocytes. Hepatology 17:869–881CrossRefGoogle Scholar
  72. Stiles AR et al (2016) Mutations in TFAM, encoding mitochondrial transcription factor A, cause neonatal liver failure associated with mtDNA depletion. Mol Genet Metab 119:91–99.  https://doi.org/10.1016/j.ymgme.2016.07.001 CrossRefPubMedGoogle Scholar
  73. Suomalainen A, Isohanni P (2010) Mitochondrial DNA depletion syndromes--many genes, common mechanisms. Neuromuscul Disord 20:429–437.  https://doi.org/10.1016/j.nmd.2010.03.017 CrossRefPubMedGoogle Scholar
  74. Suwanwela NC et al (2018) Effect of combined treatment with MLC601 (NeuroAiDTM) and rehabilitation on post-stroke recovery: the CHIMES and CHIMES-E studies. Cerebrovasc Dis 46:82–88.  https://doi.org/10.1159/000492625 CrossRefPubMedPubMedCentralGoogle Scholar
  75. Tag CG, Sauer-Lehnen S, Weiskirchen S, Borkham-Kamphorst E, Tolba RH, Tacke F, Weiskirchen R (2015) Bile duct ligation in mice: induction of inflammatory liver injury and fibrosis by obstructive cholestasis. J Vis Exp.  https://doi.org/10.3791/52438
  76. Theilen NT, Kunkel GH, Tyagi SC (2017) The role of exercise and TFAM in preventing skeletal muscle atrophy. J Cell Physiol 232:2348–2358.  https://doi.org/10.1002/jcp.25737 CrossRefPubMedPubMedCentralGoogle Scholar
  77. Tiao MM et al (2009) Early transcriptional deregulation of hepatic mitochondrial biogenesis and its consequent effects on murine cholestatic liver injury. Apoptosis 14:890–899.  https://doi.org/10.1007/s10495-009-0357-3 CrossRefPubMedGoogle Scholar
  78. Tiao MM et al (2011) Dexamethasone decreases cholestatic liver injury via inhibition of intrinsic pathway with simultaneous enhancement of mitochondrial biogenesis. Steroids 76:660–666.  https://doi.org/10.1016/j.steroids.2011.03.002 CrossRefPubMedGoogle Scholar
  79. Tormos AM, Arduini A, Talens-Visconti R, del Barco BI, Nebreda AR, Sastre J (2013) Liver-specific p38alpha deficiency causes reduced cell growth and cytokinesis failure during chronic biliary cirrhosis in mice. Hepatology 57:1950–1961.  https://doi.org/10.1002/hep.26174 CrossRefPubMedGoogle Scholar
  80. Tsai MC, Chang CP, Peng SW, Jhuang KS, Fang YH, Lin MT, Tsao TC (2015) Therapeutic efficacy of Neuro AiD (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury. J NeuroImmune Pharmacol 10:45–54.  https://doi.org/10.1007/s11481-014-9570-0 CrossRefPubMedGoogle Scholar
  81. Wang DM, Zhu QY, Ding L, Ma D (2003) Relationship between p53, bax and BCL-2 expression and cell apoptosis in intrahepatic cholestasis of pregnancy. Zhonghua Fu Chan Ke Za Zhi 38:5–7PubMedGoogle Scholar
  82. Wang GX et al (2017) DeltaNp63 inhibits oxidative stress-induced cell death, including Ferroptosis, and cooperates with the BCL-2 family to promote Clonogenic survival. Cell Rep 21:2926–2939.  https://doi.org/10.1016/j.celrep.2017.11.030 CrossRefPubMedPubMedCentralGoogle Scholar
  83. Wang K (2015) Molecular mechanisms of hepatic apoptosis regulated by nuclear factors. Cell Signal 27:729–738.  https://doi.org/10.1016/j.cellsig.2014.11.038 CrossRefPubMedGoogle Scholar
  84. Wang P et al (2019) PGC-1alpha/SNAI1 axis regulates tumor growth and metastasis by targeting miR-128b in gastric cancer. J Cell Physiol.  https://doi.org/10.1002/jcp.28193 CrossRefGoogle Scholar
  85. Wang T, Yang Z, Zhang Y, Zhang X, Wang L, Zhang S, Jia L (2018) Caspase cleavage of Mcl-1 impairs its anti-apoptotic activity and proteasomal degradation in non-small lung cancer cells. Apoptosis 23:54–64.  https://doi.org/10.1007/s10495-017-1436-5 CrossRefPubMedGoogle Scholar
  86. Wu Z et al (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124.  https://doi.org/10.1016/S0092-8674(00)80611-X CrossRefPubMedGoogle Scholar
  87. Xiang H, Kinoshita Y, Knudson CM, Korsmeyer SJ, Schwartzkroin PA, Morrison RS (1998) Bax involvement in p53-mediated neuronal cell death. J Neurosci 18:1363–1373CrossRefGoogle Scholar
  88. Yager LM, Garcia AF, Wunsch AM, Ferguson SM (2015) The ins and outs of the striatum: role in drug addiction. Neuroscience 301:529–541.  https://doi.org/10.1016/j.neuroscience.2015.06.033 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Mohammad Nasehi
    • 1
    Email author
  • Sepehr Torabinejad
    • 2
  • Mehrdad Hashemi
    • 2
  • Salar Vaseghi
    • 1
  • Mohammad-Reza Zarrindast
    • 3
    • 4
    • 5
  1. 1.Cognitive and Neuroscience Research Center (CNRC), Tehran Medical SciencesIslamic Azad UniversityTehranIran
  2. 2.Department of Genetics, Tehran Medical SciencesIslamic Azad UniversityTehranIran
  3. 3.Department of Pharmacology School of MedicineTehran University of Medical SciencesTehranIran
  4. 4.Institute for Cognitive Science Studies (ICSS)TehranIran
  5. 5.Department of Neuroendocrinology, Endocrinology and Metabolism Research InstituteTehran University of Medical SciencesTehranIran

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