Advanced SearchSearch Tips
PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative damage
facebook(new window)  Pirnt(new window) E-mail(new window) Excel Download
  • Journal title : BMB Reports
  • Volume 49, Issue 7,  2016, pp.382-387
  • Publisher : Korean Society for Biochemistry and Molecular Biology
  • DOI : 10.5483/BMBRep.2016.49.7.048
 Title & Authors
PEP-1-GSTpi protein enhanced hippocampal neuronal cell survival after oxidative damage
Sohn, Eun Jeong; Shin, Min Jea; Kim, Dae Won; Son, Ora; Jo, Hyo Sang; Cho, Su Bin; Park, Jung Hwan; Lee, Chi Hern; Yeo, Eun Ji; Choi, Yeon Joo; Yu, Yeon Hee; Kim, Duk-Soo; Cho, Sung-Woo; Kwon, Oh Shin; Cho, Yong-Jun; Park, Jinseu; Eum, Won Sik; Choi, Soo Young;
  PDF(new window)
Reactive oxygen species generated under oxidative stress are involved in neuronal diseases, including ischemia. Glutathione S-transferase pi (GSTpi) is a member of the GST family and is known to play important roles in cell survival. We investigated the effect of GSTpi against oxidative stress-induced hippocampal HT-22 cell death, and its effects in an animal model of ischemic injury, using a cell-permeable PEP-1-GSTpi protein. PEP-1-GSTpi was transduced into HT-22 cells and significantly protected against H2O2-treated cell death by reducing the intracellular toxicity and regulating the signal pathways, including MAPK, Akt, Bax, and Bcl-2. PEP-1-GSTpi transduced into the hippocampus in animal brains, and markedly protected against neuronal cell death in an ischemic injury animal model. These results indicate that PEP-1-GSTpi acts as a regulator or an antioxidant to protect against oxidative stress-induced cell death. Our study suggests that PEP-1-GSTpi may have potential as a therapeutic agent for the treatment of ischemia and a variety of oxidative stress-related neuronal diseases.
Apoptotic signals;Ischemia;Oxidative stress;PEP-1-GSTpi;Protein therapy;
 Cited by
Udomsinprasert R, Pongjaroenkit S, Wongsantichon J et al (2005) Identification, characterization and structure of a new delta class glutathione transferase isoenzyme. Biochem J 388, 763-771 crossref(new window)

Sheehan D, Meade G, Foley VM and Dowd CA (2001) Structure, function and evolution of glutathione transferases: implications for classification of non-mammalian members of an ancient enzyme superfamily. Biochem J 36, 1-16 crossref(new window)

Raza H (2011) Dual localization of glutathione S-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. FEBS J 278, 4243-4251 crossref(new window)

Atkinson HJ and Babbitt PC (2009) Glutathione transferases are structural and functional outliers in the thioredoxin fold. Biochemistry 48, 11108-11116 crossref(new window)

Harrison DJ, Kharbanda R, Cunningham DS, McLellan LI and Hayes JD (1989) Distribution of glutathione S-transferase isoenzymes in human kidney: basis for possible markers of renal injury. J Clin Pathol 42, 624-628 crossref(new window)

Landi S (2000) Mammalian class theta GST and differential susceptibility to carcinogens: a review. Mutat Res 463, 247-283 crossref(new window)

Townsend DM and Tew KD (2003) The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene 22, 7369-7375 crossref(new window)

Mari M, Morales A, Colell A, Garcia-Ruiz C and Fernandez-Checa JC (2009) Mitochondrial glutathione, a key survival antioxidant. Antioxid Redox Signal 11, 2685-2700 crossref(new window)

Tew KD and Ronai Z (1999) GST function in drug and stress response. Drug Resist Updat 2, 143-147 crossref(new window)

Laborde E (2010) Glutathione transferases as mediators of signaling pathways involved in cell proliferation and cell death. Cell Death Differ 17, 1373-1380 crossref(new window)

Thevenin AF, Zony CL, Bahnson BJ and Colman RF (2011) GSTpi modulates JNK activity through a direct interaction with JNK substrate, ATF2. Protein Sci 20, 834-848 crossref(new window)

Wu Y, Fan Y, Xue B et al (2006) Human glutathione S-transferase P1-1 interacts with TRAF2 and regulates TRAF2–ASK1 signals. Oncogene 25, 5787-5800 crossref(new window)

Misra MK, Sarwat M, Bhakuni P et al (2009) Oxidative stress and ischemic myocardial syndromes. Med Sci Monit 15, RA209-RA219

Halliwell B (2006) Oxidative stress and neurodegeneration: where are we now? J Neurochem 97, 1634-1658 crossref(new window)

Giorgio M, Trinei M, Migliaccio E and Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat RevMol Cell Biol 8, 722-728 crossref(new window)

Coyle JT and Puttfarcken P (1993) Oxidative stress, glutamate, and neurodegenerative disorders. Science 262, 689-695 crossref(new window)

Kleikers PW, Wingler K, Hermans JJ et al (2012) NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury. J Mol Med 90, 1391-1406 crossref(new window)

Moro MA, Almeida A, Bolanos JP and Lizasoain I (2005) Mitochondrial respiratory chain and free radical generation in stroke. Free Radic Biol Med 39, 1291-1304 crossref(new window)

Atlante A, Bobba A, Calissano P, Passarella S and Marra E (2003) The apoptosis/necrosis transition in cerebellar granule cells depends on the mutual relationship of the antioxidant and the proteolytic systems which regulate ROS production and cytochrome c release enroute to death. J Neurochem 84, 960-971 crossref(new window)

Jay SM and Lee RT (2013) Protein engineering for cardiovascular therapeutics: untapped potential for cardiac repair. Circ Res 113, 933-943 crossref(new window)

Koren E and Torchilin VP (2012) Cell-penetrating peptides: breaking through to the other side. Trends Mol Med 18, 385-393 crossref(new window)

Gump JM and Dowdy SF (2007) TAT transduction: the molecular mechanism and therapeutic prospects. Trends Mol Med 13, 443-448 crossref(new window)

Brooks NA, Pouniotis DS, Tang CK, Apostolopoulos V and Pietersz GA (2010) Cell penetrating peptides: application in vaccine delivery. Biochim Biophys Acta 1805, 25-34

Woo SJ, Shin MJ, Kim DW et al (2015) Effects of low doses of Tat-PIM2 protein against hippocampal neuronal cell survival. J Neurol Sci 358, 226-235 crossref(new window)

Kim MJ, Park M, Kim DW et al (2015) Transduced PEP-1-PON1 proteins regulate microglial activation and dopaminergic neuronal death in a Parkinson's disease model. Biomaterials 64, 45-56 crossref(new window)

Jeong HJ, Yoo DY, Kim DW et al (2014) Neuroprotective effect of PEP-1-peroxiredoxin2 on CA1 regions in the hippocampus against ischemic insult. Biochim Biophys Acta 1840, 2321-2330 crossref(new window)

Luo L, Wang Y, Feng Q et al (2009) Recombinant protein glutathione S-transferases P1 attenuates inflammation in mice. Mol Immunol 46, 848-857 crossref(new window)

Townsend DM, Manevich Y, He L, Hutchens S, Pazoles CJ and Tew KD (2009) Novel role for glutathione S-transferase pi: regulator of protein S-glutathionylation following oxidative and nitrosative stress. J Biol Chem 284, 436-445 crossref(new window)

Ramsey JD and Flynn NH (2015) Cell-penetrating peptides transport therapeutics into cells. Pharmacol Therapeut 154, 78-86 crossref(new window)

Dietz (2010) Cell penetrating peptide technology to delivery chaperones and associated factors in diseases and basic research. Curr Pharm Biotechnol 11, 167-174 crossref(new window)

Lei B, Adachi N and Arai T (1998) Measurement of the extracellular H2O2 in the brain by microdialysis. Brain Res Brain Res Protoc 3, 33-36 crossref(new window)

Liu D, Liu J and Wen J (1999) Elevation of hydrogen peroxide after spinal cord injury detected by using the Fenton reaction. Free Radic Biol Med 27, 478-482 crossref(new window)

Zhou L, Jing Y, Styblo M, Chen Z and Waxman S (2005) Glutathion-S-transferase π inhibits As2O3-induced apoptosis in lymphoma cells: involvement of hydrogen peroxided catabolism. Blood 105, 1198-1203 crossref(new window)

Ohashi M, Hirano T, Watanabe K et al (2016) Hydrogen peroxide modulates synaptic transmission in ventral horn neurons of the rat spinal cord. J Physiol 594, 115-134 crossref(new window)

Prasad SS, Russell M and Nowakowska M (2011) Neuroprotection induced in vitro by ischemic preconditioning and postconditioning: modulation of apoptosis and PI3K–Akt pathways. J Mol Neurosci 43, 428-442 crossref(new window)

Adler V, Yin Z and Fuchs SY (1999) Regulation of JNK signaling by GSTpi. EMBO J 18, 1321-1334 crossref(new window)

Kwon SH, Hong SI, Kim JA et al (2011) The neuroprotective effects of Lonicera japonica THUNB. against hydrogen peroxide-induced apoptosis via phosphorylation of MAPKs and PI3K/Akt in SH-SY5Y cells. Food Chem Toxicol 49, 1011-1019 crossref(new window)

Higgins GC, Beart PM, Shin YS, Chen MJ, Cheung NS and Nagley P (2010) Oxidative stress: emerging mitochondrial and cellular themes and variations in neuronal injury. J Alzheimers Dis 20, 453-473 crossref(new window)

Choi WS, Canzoniero LM, Sensi SL et al (1999) Characterization of MPP+-induced cell death in a dopaminergic neuronal cell line : role of macromolecule synthesis, cytosolic calcium, caspase, and Bcl-2-related proteins. Exp Neurol 159, 274-282 crossref(new window)

Fuenzalida K, Quintanilla R, Ramos P et al (2007) Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces apoptosis. J Biol Chem 282, 37006-37015 crossref(new window)

Castro-Caldas M, Milagre I, Rodrigues E and Gama MJ (2009) Glutathion S-transferase pi regulates UV-induced JNK signaling in SH-SY5Y neuroblastoma cells. Neurosci Lett 451, 241-245 crossref(new window)

Castro-Caldas M, Nerves-Carvalho A, Peixeiro I, Rodrigues E, Lechner MC and Gama MJ (2009) GSTpi expression in MPTP-induced dopaminergic neurodegeneration of C57BL/6 mouse midbrain and striatum. J Mol Neurosci 38, 114-127 crossref(new window)

Bradford MA (1976) A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72, 248-254 crossref(new window)

Kim YN, Jung HY, Eum WS et al (2014) Neuroprotective effects of PEP-1-carbonyl reductase 1 against oxidative stress-induced ischemic neuronal cell damage. Free Radic Biol Med 69, 181-196 crossref(new window)