Abstract
In a previous study, we observed a significant increase in phosphoglycerate mutase 1 (PGAM1) levels after pyridoxine treatment. In the present study, we investigated the effects of PGAM1 on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. We generated a Tat-PGAM1 fusion protein to cross the blood–brain barrier and neuronal plasma membrane. We administered the Tat peptide, control-PGAM1, or Tat-PGAM1 fusion protein to 8-week-old mice once a day for 3 weeks and tested novel object recognition memory. The mice were then euthanized to conduct western blot analysis for polyhistidine expression and immunohistochemical analysis for Ki67, doublecortin, and phosphorylated cAMP response element-binding protein. Mice treated with Tat peptide showed similar exploration times for familiar and new objects and the discrimination index was significantly lower in this group than in the control group. Tat-PGAM1 moderately increased the exploration time of new objects when compared to familiar objects, while the discrimination index was significantly higher in the Tat-PGAM1-treated group, but not in the control-PGAM1-treated group, when compared with the control group. Higher PGAM1 protein expression was observed in the hippocampus of Tat-PGAM1-treated mice when compared with the hippocampi of control, Tat peptide-, and control-PGAM1-treated mice, using western blot analysis. In addition, the numbers of proliferating cells and differentiated neuroblasts were significantly lower in the Tat peptide-treated group than in the control group. In contrast, the numbers of proliferating cells and differentiated neuroblasts in the dentate gyrus were higher in the Tat-PGAM1-treated group than in the control group. Administration of Tat-PGAM1 significantly facilitated the phosphorylation of cAMP response element-binding protein in the dentate gyrus. Administration of control-PGAM1 did not show any significant effects on novel object recognition, cell proliferation, and neuroblast differentiation in the dentate gyrus. These results suggest that PGAM1 plays a role in cell proliferation and neuroblast differentiation in the dentate gyrus via the phosphorylation of cAMP response element-binding protein in the hippocampus.
Similar content being viewed by others
Data Availability
The datasets and supporting materials generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Kempermann G, Gage FH (1999) New nerve cells for the adult brain. Sci Am 280:48–53
Drew LJ, Fusi S, Hen R (2013) Adult neurogenesis in the mammalian hippocampus: why the dentate gyrus? Learn Mem 20:710–729
Kee N, Teixeira CM, Wang AH, Frankland PW (2007) Preferential incorporation of adult-generated granule cells into spatial memory networks in the dentate gyrus. Nat Neurosci 10:355–362
Dupret D, Revest JM, Koehl M et al (2008) Spatial relational memory requires hippocampal adult neurogenesis. PLoS ONE 3:e1959
Rikani AA, Choudhry Z, Choudhry AM, Zenonos G, Tariq S, Mobassarah NJ (2013) Spatially regulated adult neurogenesis. Ann Neurosci 20:67–70
Bond AM, Ming GL, Song H (2015) Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell 17:385–395
Fothergill-Gilmore LA, Watson HC (1989) The phosphoglycerate mutases. Adv Enzymol Relat Areas Mol Biol 62:227–313
Usuba T, Ishibashi Y, Okawa Y, Hirakawa T, Takada K, Ohkawa K (2001) Purification and identification of monoubiquitin-phosphoglycerate mutase B complex from human colorectal cancer tissues. Int J Cancer 94:662–668
Li C, Xiao Z, Chen Z et al (2006) Proteome analysis of human lung squamous carcinoma. Proteomics 6:547–558
Durany N, Joseph J, Jimenez OM et al (2000) Phosphoglycerate mutase, 2,3-bisphosphoglycerate phosphatase, creatine kinase and enolase activity and isoenzymes in breast carcinoma. Br J Cancer 82:20–27
Fang MZ, Liu C, Song Y et al (2004) Over-expression of gastrin-releasing peptide in human esophageal squamous cell carcinomas. Carcinogenesis 25:865–871
Turhani D, Krapfenbauer K, Thurnher D, Langen H, Fountoulakis M (2006) Identification of differentially expressed, tumor-associated proteins in oral squamous cell carcinoma by proteomic analysis. Electrophoresis 27:1417–1423
Gao H, Yu B, Yan Y et al (2013) Correlation of expression levels of ANXA2, PGAM1, and CALR with glioma grade and prognosis. J Neurosurg 118:846–853
Jain R, Kulkarni P, Dhali S, Rapole S, Srivastava S (2015) Quantitative proteomic analysis of global effect of LLL12 on U87 cell’s proteome: an insight into the molecular mechanism of LLL12. J Proteomics 113:127–142
Xu Z, Gong J, Wang C et al (2016) The diagnostic value and functional roles of phosphoglycerate mutase 1 in glioma. Oncol Rep 36:2236–2244
Liu ZG, Ding J, Du C et al (2018) Phosphoglycerate mutase 1 is highly expressed in C6 glioma cells and human astrocytoma. Oncol Lett 15:8935–8940
Ren F, Wu H, Lei Y et al (2010) Quantitative proteomics identification of phosphoglycerate mutase 1 as a novel therapeutic target in hepatocellular carcinoma. Mol Cancer 9:81
Hitosugi T, Zhou L, Elf S et al (2012) Phosphoglycerate mutase 1 coordinates glycolysis and biosynthesis to promote tumor growth. Cancer Cell 22:585–600
Scatena R, Bottoni P, Pontoglio A, Mastrototaro L, Giardina B (2008) Glycolytic enzyme inhibitors in cancer treatment. Expert Opin Investig Drugs 17:1533–1545
Jacobowitz DM, Jozwik C, Fukuda T, Pollard HB (2008) Immunohistochemical localization of Phosphoglycerate mutase in capillary endothelium of the brain and periphery. Microvasc Res 76:89–93
Imperlini E, Orrù S, Corbo C, Daniele A, Salvatore F (2014) Altered brain protein expression profiles are associated with molecular neurological dysfunction in the PKU mouse model. J Neurochem 129:1002–1012
Sharma NK, Sethy NK, Bhargava K (2013) Comparative proteome analysis reveals differential regulation of glycolytic and antioxidant enzymes in cortex and hippocampus exposed to short-term hypobaric hypoxia. J Proteomics 79:277–298
Martins-de-Souza D, Alsaif M, Ernst A et al (2012) The application of selective reaction monitoring confirms dysregulation of glycolysis in a preclinical model of schizophrenia. BMC Res Notes 5:146
Prabakaran S, Swatton JE, Ryan MM et al (2004) Mitochondrial dysfunction in schizophrenia: evidence for compromised brain metabolism and oxidative stress. Mol Psychiatry 9:684–697
Zhang D, Jin N, Sun W et al (2017) Phosphoglycerate mutase 1 promotes cancer cell migration independent of its metabolic activity. Oncogene 36:2900–2909
Yoo DY, Kim W, Kim DW et al (2011) Pyridoxine enhances cell proliferation and neuroblast differentiation by upregulating the GABAergic system in the mouse dentate gyrus. Neurochem Res 36:713–721
Jung HY, Kim DW, Nam SM et al (2017) Pyridoxine improves hippocampal cognitive function via increases of serotonin turnover and tyrosine hydroxylase, and its association with CB1 cannabinoid receptor-interacting protein and the CB1 cannabinoid receptor pathway. Biochim Biophys Acta 1861:3142–3153
Liebner S, Dijkhuizen RM, Reiss Y, Plate KH, Agalliu D, Constantin G (2018) Functional morphology of the blood-brain barrier in health and disease. Acta Neuropathol 135:311–336
Daneman R (2012) The blood-brain barrier in health and disease. Ann Neurol 72:648–672
Green M, Loewenstein PM (1988) Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 55:1179–1188
Frankel AD, Pabo CO (1988) Cellular uptake of the tat protein from human immunodeficiency virus. Cell 55:1189–1193
Eum WS, Kim DW, Hwang IK et al (2004) In vivo protein transduction: biologically active intact pep-1-superoxide dismutase fusion protein efficiently protects against ischemic insult. Free Radic Biol Med 37:1656–1669
Yoo DY, Kim DW, Kwon HJ et al (2017) Chronic administration of SUMO1 has negative effects on novel object recognition memory as well as cell proliferation and neuroblasts differentiation in the mouse dentate gyrus. Mol Med Rep 16:3427–3432
Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG (2010) Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol 8:e1000412
Kwon HY, Eum WS, Jang HW et al (2000) Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1Tat protein basic domain into mammalian cells. FEBS Lett 485:163–167
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of proteindye binding. Anal Biochem 72:248254
Paxinos G, Franklin KBJ (2001) The mouse brain in stereotaxic coordinates. Academic Press, San Diego
Cortesi L, Barchetti A, De Matteis E et al (2009) Identification of protein clusters predictive of response to chemotherapy in breast cancer patients. J Proteome Res 8:4916–4933
Buccarello L, Borsello T (2017) The Tat-Aβ1-6A2V(D) peptide against AD synaptopathy. Oncotarget 8:10773–10774
Tu J, Zhang X, Zhu Y et al (2015) Cell-permeable peptide targeting the Nrf2-Keap1 interaction: a potential novel therapy for global cerebral ischemia. J Neurosci 35:14727–14739
Kim SM, Hwang IK, Yoo DY et al (2015) Tat-antioxidant 1 protects against stress-induced hippocampal HT-22 cells death and attenuate ischaemic insult in animal model. J Cell Mol Med 19:1333–1345
Gannon P, Khan MZ, Kolson DL (2011) Current understanding of HIV-associated neurocognitive disorders pathogenesis. Curr Opin Neurol 24:275–283
Irish BP, Khan ZK, Jain P et al (2009) Molecular mechanisms of neurodegenerative diseases induced by human retroviruses: a review. Am J Infect Dis 5:231–258
Ferrell D, Giunta B (2014) The impact of HIV-1 on neurogenesis: implications for HAND. Cell Mol Life Sci 71:4387–4392
Fan Y, Gao X, Chen J, Liu Y, He JJ (2016) HIV Tat impairs neurogenesis through functioning as a Notch ligand and activation of Notch signaling pathway. J Neurosci 36:11362–11373
Harricharan R, Thaver V, Russell VA, Daniels WM (2015) Tat-induced histopathological alterations mediate hippocampus-associated behavioural impairments in rats. Behav Brain Funct 11:3
Lonze BE, Riccio A, Cohen S, Ginty DD (2002) Apoptosis, axonal growth defects, and degeneration of peripheral neurons in mice lacking CREB. Neuron 34:371–385
Redmond L, Kashani AH, Ghosh A (2002) Calcium regulation of dendritic growth via CaM kinase IV and CREB-mediated transcription. Neuron 34:999–1010
Segarra-Mondejar M, Casellas-Díaz S, Ramiro-Pareta M et al (2018) Synaptic activity-induced glycolysis facilitates membrane lipid provision and neurite outgrowth. EMBO J 37(9):e97368
Yoo DY, Lee KY, Park JH et al (2016) Glucose metabolism and neurogenesis in the gerbil hippocampus after transient forebrain ischemia. Neural Regen Res 11:1254–1259
Jung HY, Yim HS, Yoo DY et al (2016) Postnatal changes in glucose transporter 3 expression in the dentate gyrus of the C57BL/6 mouse model. Lab Anim Res 32:1–7
Yoo DY, Kim W, Yoo KY et al (2012) Effects of pyridoxine on a high-fat diet-induced reduction of cell proliferation and neuroblast differentiation depend on cyclic adenosine monophosphate response element binding protein in the mouse dentate gyrus. J Neurosci Res 90:1615–1625
Acknowledgements
This work was supported by the Promising-Pioneering Researcher Program through Seoul National University (SNU) in 2015 and by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIP) (Nos. NRF-2016R1A2B4009156 and NRF-2018R1A2B6001941). In addition, this study was partially supported by the Research Institute for Veterinary Science of Seoul National University.
Author information
Authors and Affiliations
Contributions
HYJ, HJK, WK, SMN, JWK, KRH, DYY, MHW, YSY, DWK, and IKH conceived the study. HYJ, HJK, DWK, and IKH designed the study and wrote the manuscript. HYJ, WK, JWK, and KRH conducted the animal experiments and HJK and DWK conducted biochemical experiments. SMN, DYY, MHW, and YSY participated in designing and critical discussing the study. All authors have read and approved the final manuscript.
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no competing interests.
Rights and permissions
About this article
Cite this article
Jung, H.Y., Kwon, H.J., Kim, W. et al. Phosphoglycerate Mutase 1 Promotes Cell Proliferation and Neuroblast Differentiation in the Dentate Gyrus by Facilitating the Phosphorylation of cAMP Response Element-Binding Protein. Neurochem Res 44, 323–332 (2019). https://doi.org/10.1007/s11064-018-2678-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-018-2678-5