PEP-1-HO-1 prevents MPTP-induced degeneration of dopaminergic neurons in a Parkinson’s disease mouse model
2
조회
0
다운로드
2
인용
0
참고문헌
키워드
초록
Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide,biliverdin, and Fe2+, which play important roles in variousbiochemical processes. In this study, we examined theprotective function of HO-1 against oxidative stress in SH-SY5Ycells and in a Parkinson’s disease mouse model. Western blotand fluorescence microscopy analysis demonstrated thatPEP-1-HO-1, fused with a PEP-1 peptide can cross the cellularmembranes of human neuroblastoma SH-SY5Y cells. Inaddition, the transduced PEP-1-HO-1 inhibited generation ofreactive oxygen species (ROS) and cell death caused by1-methyl-4-phenylpyridinium ion (MPP+). In contrast, HO-1,which has no ability to transduce into SH-SY5Y cells, failed toreduce MPP+-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed theblood-brain barrier in mouse brains. In a PD mouse model,PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergicneuronal death. Therefore, PEP-1-HO-1 could be auseful agent in treating oxidative stress induced ailmentsincluding PD.
Abstract
Heme oxygenase-1 (HO-1) degrades heme to carbon dioxide,biliverdin, and Fe2+, which play important roles in variousbiochemical processes. In this study, we examined theprotective function of HO-1 against oxidative stress in SH-SY5Ycells and in a Parkinson’s disease mouse model. Western blotand fluorescence microscopy analysis demonstrated thatPEP-1-HO-1, fused with a PEP-1 peptide can cross the cellularmembranes of human neuroblastoma SH-SY5Y cells. Inaddition, the transduced PEP-1-HO-1 inhibited generation ofreactive oxygen species (ROS) and cell death caused by1-methyl-4-phenylpyridinium ion (MPP+). In contrast, HO-1,which has no ability to transduce into SH-SY5Y cells, failed toreduce MPP+-induced cellular toxicity and ROS production. Furthermore, intraperitoneal injected PEP-1-HO-1 crossed theblood-brain barrier in mouse brains. In a PD mouse model,PEP-1-HO-1 significantly protected against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced toxicity and dopaminergicneuronal death. Therefore, PEP-1-HO-1 could be auseful agent in treating oxidative stress induced ailmentsincluding PD.
참고문헌 (25)
- Weinreb, O., "Targeting dysregulation of brain iron homeostasis in Parkinson's disease by iron chelators", Free Radic. Biol. Med, 62, pp.52~64 (2013)
- Morse, D., "Heme oxygenase-1: the "emerging molecule" has arrived", Am. J. Respir. Cell. Mol. Biol, 27, pp.8~16 (2002)
- Grochot-Przeczek, A., "Haem oxygenase-1: non-canonical roles in physiology and pathology", Clin. Sci. (Lond), 122, pp.93~103 (2012)
- Innamorato, N. G., "Different susceptibility to the Parkinson's toxin MPTP in mice lacking the redox master regulator Nrf2 or its target gene heme oxygenase-1", PLoS One, 5, pp.e11838~ (2010)
- Morris, M. C., "A peptide carrier for the delivery of biologically active proteins into mammalian cells", Nat. Biotechnol, 19, pp.1173~1176 (2001)
- Brouard, S., "Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis", J. Exp. Med, 192, pp.1015~1026 (2000)
- Baranano, D. E., "Biliverdin reductase: a major physiologic cytoprotectant", Proc. Natl. Acad. Sci. U.S.A, 99, pp.16093~16098 (2002)
- Oberle, S., "The antioxidant defense protein ferritin is a novel and specific target for pentaerithrityl tetranitrate in endothelial cells", Biochem. Biophys. Res. Commun, 261, pp.28~34 (1999)
- Kwon, S. W., "Anti-inflammatory effect of transduced PEP-1-heme oxygenase- 1 in Raw 264.7 cells and a mouse edema model", Biochem. Biophys. Res. Commun, 411, pp.354~359 (2011)
- Wadia, J. S., "Protein transduction technology", Curr. Opin. Biotechnol, 13, pp.52~56 (2002)
- Ahn, E. H., "PEP-1-ribosomal protein S3 protects dopaminergic neurons in an MPTP-induced Parkinson's disease mouse model", Free Radic. Biol. Med, 55, pp.36~45 (2013)
- 이선화, "Suppression of 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced skin inflammation in mice by transduced Tat-Annexin protein", BMB Reports, 45(6), pp.354~359 (2012), 생화학분자생물학회
- Miller, R. L., "Oxidative and inflammatory pathways in Parkinson's disease", Neurochem. Res, 34, pp.55~65 (2009)
- Blandini, F., "Animal models of Parkinson's disease", FEBS J, 279, pp.1156~1166 (2012)
- Schipper, H. M., "Heme oxygenase expression in human central nervous system disorders", Free Radic. Biol. Med, 37, pp.1995~2011 (2004)
- Schipper, H. M., "Heme oxygenase-1: role in brain aging and neurodegeneration", Exp. Gerontol, 35, pp.821~830 (2000)
- Tronel, C., "Oxidative stress is related to the deleterious effects of heme oxygenase-1 in an in vivo neuroinflammatory rat model", Oxid. Med. Cell Longev, 2013 (2013)
- Panahian, N., "Overexpression of heme oxygenase-1 is neuroprotective in a model of permanent middle cerebral artery occlusion in transgenic mice", J. Neurochem, 72, pp.1187~1203 (1999)
- Chen, K., "Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death", J. Neurochem, 75, pp.304~313 (2000)
- Hung, S. Y., "Overexpression of heme oxygenase- 1 protects dopaminergic neurons against 1-methyl-4- phenylpyridinium-induced neurotoxicity", Mol. Pharmacol, 74, pp.1564~1575 (2008)
- Chen-Roetling, J., "Cultured astrocytes from heme oxygenase-1 knockout mice are more vulnerable to heme-mediated oxidative injury", J. Neurosci. Res, 82, pp.802~810 (2005)
- Zeynalov, E., "Heme oxygenase 1 is associated with ischemic preconditioning- induced protection against brain ischemia", Neurobiol. Dis, 35, pp.264~269 (2009)
- Jeong, G. S., "Neuroprotective and anti- inflammatory effects of mollugin via up-regulation of heme oxygenase-1 in mouse hippocampal and microglial cells", Eur. J. Pharmacol, 654, pp.226~234 (2011)
- 김덕수, "PEP-1-p18 prevents neuronal cell death by inhibiting oxidative stress and Bax expression", BMB Reports, 45(9), pp.532~537 (2012), 생화학분자생물학회
- Ahn, E. H., "Transduced PEP-1-ribosomal protein S3 (rpS3) ameliorates 12-O-tetradecanoylphorbol- 13-acetate-induced inflammation in mice", Toxicol, 276, pp.192~197 (2010)