The presence of pyruvate carboxylase in the human brain and its role in the survival of cultured human astrocytes
Jazyk angličtina Země Česko Médium print
Typ dokumentu časopisecké články
PubMed
37449752
PubMed Central
PMC10669001
DOI
10.33549/physiolres.935026
PII: 935026
Knihovny.cz E-zdroje
- MeSH
- astrocyty * metabolismus MeSH
- kyselina pyrohroznová metabolismus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurony metabolismus MeSH
- pyruvátkarboxylasa * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- kyselina pyrohroznová MeSH
- pyruvátkarboxylasa * MeSH
Pyruvate carboxylase (PC) is a mitochondrial, biotin-containing enzyme catalyzing the ATP-dependent synthesis of oxaloacetate from pyruvate and bicarbonate, with a critical anaplerotic role in sustaining the brain metabolism. Based on the studies performed on animal models, PC expression was assigned to be glia-specific. To study PC distribution among human neural cells, we probed the cultured human astrocytes and brain sections with antibodies against PC. Additionally, we tested the importance of PC for the viability of cultured human astrocytes by applying the PC inhibitor 3-chloropropane-1,2-diol (CPD). Our results establish the expression of PC in mitochondria of human astrocytes in culture and brain tissue and also into a subpopulation of the neurons in situ. CPD negatively affected the viability of astrocytes in culture, which could be partially reversed by supplementing media with malate, 2-oxoglutarate, citrate, or pyruvate. The provided data estimates PC expression in human astrocytes and neurons in human brain parenchyma. Furthermore, the enzymatic activity of PC is vital for sustaining the viability of cultured astrocytes.
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Inigo M, Deja S, Burgess SC. Ins and outs of the TCA cycle: the central role of anaplerosis. Annu Rev Nutr. 2021;41:19–47. doi: 10.1146/annurev-nutr-120420-025558. PubMed DOI
Owen OE, Kalhan SC, Hanson RW. The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem. 2002;277:30409–30412. doi: 10.1074/jbc.R200006200. PubMed DOI
LAJTHA A, GIBSON GE, DIENEL GA, editors. Handbook of Neurochemistry and Molecular Neurobiology. Springer; US, Boston, MA: 2007. Hassel B: 3.1 Anaplerosis; pp. 183–195. DOI
Schousboe A, Waagepetersen HS, Sonnewald U. Astrocytic pyruvate carboxylation: Status after 35 years. J Neurosci Res. 2019;97:890–896. doi: 10.1002/jnr.24402. PubMed DOI
Wang D, De Vivo D. Pyruvate carboxylase deficiency. In: ADAM MP, ARDINGER HH, PAGON RA, et al., editors. GeneReviews®. University of Washington; Seattle, Seattle (WA): 1993.
Brun N, Robitaille Y, Grignon A, Robinson BH, Mitchell GA, Lambert M. Pyruvate carboxylase deficiency: prenatal onset of ischemia-like brain lesions in two sibs with the acute neonatal form. Am J Med Genet. 1999;84:94–101. doi: 10.1002/(SICI)1096-8628(19990521)84:2<94::AID-AJMG3>3.0.CO;2-1. PubMed DOI
García-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P, Saudubray J-M. Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. Ann Neurol. 2006;59:121–127. doi: 10.1002/ana.20709. PubMed DOI
Hidalgo J, Campoverde L, Ortiz JF, Ruxmohan S, Eissa-Garcés A. A unique case of pyruvate carboxylase deficiency. Cureus. 2021;13:e15042. doi: 10.7759/cureus.15042. PubMed DOI PMC
Mhanni AA, Rockman-Greenberg C, Ryner L, Bunge M. Prenatal onset of the neuroradiologic phenotype of pyruvate carboxylase deficiency due to homozygous PC c.1828G > A mutations. JIMD Rep. 2021;61:42–47. doi: 10.1002/jmd2.12235. PubMed DOI PMC
Mochel F, DeLonlay P, Touati G, Brunengraber H, Kinman RP, Rabier D, Roe CR, Saudubray J-M. Pyruvate carboxylase deficiency: clinical and biochemical response to anaplerotic diet therapy. Mol Genet Metab. 2005;84:305–312. doi: 10.1016/j.ymgme.2004.09.007. PubMed DOI
Monnot S, Serre V, Chadefaux-Vekemans B, Aupetit J, Romano S, De Lonlay P, Rival J-M, et al. Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. Hum Mutat. 2009;30:734–740. doi: 10.1002/humu.20908. PubMed DOI
Schiff M, Levrat V, Acquaviva C, Vianey-Saban C, Rolland M-O, Guffon N. A case of pyruvate carboxylase deficiency with atypical clinical and neuroradiological presentation. Mol Genet Metab. 2006;87:175–177. doi: 10.1016/j.ymgme.2005.10.007. PubMed DOI
Pardridge WM. Brain metabolism: a perspective from the blood-brain barrier. Physiol Rev. 1983;63:1481–1535. doi: 10.1152/physrev.1983.63.4.1481. PubMed DOI
Gruetter R, Novotny EJ, Boulware SD, Mason GF, Rothman DL, Shulman GI, Prichard JW, Shulman RG. Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J Neurochem. 1994;63:1377–1385. doi: 10.1046/j.1471-4159.1994.63041377.x. PubMed DOI
Hertz L, Chen Y. Integration between glycolysis and glutamate-glutamine cycle flux may explain preferential glycolytic increase during brain activation, requiring glutamate. Front Integr Neurosci. 2017;11:18. doi: 10.3389/fnint.2017.00018. PubMed DOI PMC
Gray LR, Tompkins SC, Taylor EB. Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci. 2014;71:2577–2604. doi: 10.1007/s00018-013-1539-2. PubMed DOI PMC
Shank RP, Bennett GS, Freytag SO, Campbell GL. Pyruvate carboxylase: an astrocyte-specific enzyme implicated in the replenishment of amino acid neurotransmitter pools. Brain Res. 1985;329:364–367. doi: 10.1016/0006-8993(85)90552-9. PubMed DOI
Shank RP, Leo GC, Zielke HR. Cerebral metabolic compartmentation as revealed by nuclear magnetic resonance analysis of D-[1-13C]glucose metabolism. J Neurochem. 1993;61:315–323. doi: 10.1111/j.1471-4159.1993.tb03570.x. PubMed DOI
Cesar M, Hamprecht B. Immunocytochemical examination of neural rat and mouse primary cultures using monoclonal antibodies raised against pyruvate carboxylase. J Neurochem. 1995;64:2312–2318. doi: 10.1046/j.1471-4159.1995.64052312.x. PubMed DOI
Murín R, Cesar M, Kowtharapu BS, Verleysdonk S, Hamprecht B. Expression of pyruvate carboxylase in cultured oligodendroglial, microglial and ependymal cells. Neurochem Res. 2009;34:480–489. doi: 10.1007/s11064-008-9806-6. PubMed DOI
Amaral AI, Hadera MG, Tavares JM, Kotter MRN, Sonnewald U. Characterization of glucose-related metabolic pathways in differentiated rat oligodendrocyte lineage cells. Glia. 2016;64:21–34. doi: 10.1002/glia.22900. PubMed DOI PMC
Salganicoff L, Koeppe RE. Subcellular distribution of pyruvate carboxylase, diphosphopyridine nucleotide and triphosphopyridine nucleotide isocitrate dehydrogenases, and malate enzyme in rat brain. J Biol Chem. 1968;243:3416–3420. doi: 10.1016/S0021-9258(18)93324-7. PubMed DOI
Hassel B. Carboxylation and anaplerosis in neurons and glia. Mol Neurobiol. 2000;22:21–40. doi: 10.1385/MN:22:1-3:021. PubMed DOI
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–254. doi: 10.1006/abio.1976.9999. PubMed DOI
Gondáš E, Král’ová Trančíková A, Majerčíková Z, Pokusa M, Baranovičová E, Bystrický P, Dobrota D, Murín R. Expression of pyruvate carboxylase in cultured human astrocytoma, glioblastoma and neuroblastoma cells. Gen Physiol Biophys. 2021;40:127–135. doi: 10.4149/gpb_2021003. PubMed DOI
Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65:55–63. doi: 10.1016/0022-1759(83)90303-4. PubMed DOI
Warren GB, Tipton KF. Pig liver pyruvate carboxylase. Purification, properties and cation specificity. Biochem J. 1974;139:297–310. doi: 10.1042/bj1390297. PubMed DOI PMC
Gondáš E, Král’ová Trančíková A, Dibdiaková K, Galanda T, Hatok J, Račay P, Dobrota D, Murín R. Immunodetection of pyruvate carboxylase expression in human astrocytomas, glioblastomas, oligodendrogliomas, and meningiomas. Neurochem Res. 2023;48:1728–1736. doi: 10.1007/s11064-023-03856-5. PubMed DOI PMC
Doedens D, Ashmore J. Inhibition of pyruvate carboxylase by chloropyruvic acid and related compounds. Biochem Pharmacol. 1972;21:1745–1751. doi: 10.1016/0006-2952(72)90081-0. PubMed DOI
Zeczycki TN, St Maurice M, Attwood PV. Inhibitors of pyruvate carboxylase. Open Enzyme Inhib J. 2010;3:8–26. doi: 10.2174/1874940201003010008. PubMed DOI PMC
Atkin BM, Buist NRM, Utter MF, Leiter AB, Banker BQ. Pyruvate carboxylase deficiency and lactic acidosis in a retarded child without Leigh’s disease. Pediatr Res. 1979;13:109–116. doi: 10.1203/00006450-197902000-00005. PubMed DOI
Zhang Z, Ma Z, Zou W, Guo H, Liu M, Ma Y, Zhang L. The appropriate marker for astrocytes: comparing the distribution and expression of three astrocytic markers in different mouse cerebral regions. Biomed Res Int. 2019;2019:1–15. doi: 10.1155/2019/9605265. PubMed DOI PMC
Yu AC, Drejer J, Hertz L, Schousboe A. Pyruvate carboxylase activity in primary cultures of astrocytes and neurons. J Neurochem. 1983;41:1484–1487. doi: 10.1111/j.1471-4159.1983.tb00849.x. PubMed DOI
Yuan A, Rao MV, Veeranna Nixon RA. Neurofilaments and neurofilament proteins in health and disease. Cold Spring Harb Perspect Biol. 2017;9:a018309. doi: 10.1101/cshperspect.a018309. PubMed DOI PMC
Hassel B, Bråthe A. Neuronal pyruvate carboxylation supports formation of transmitter glutamate. J Neurosci. 2000;20:1342–1347. doi: 10.1523/JNEUROSCI.20-04-01342.2000. PubMed DOI PMC
Hassel B, Bråthe A. Cerebral metabolism of lactate in vivo: evidence for neuronal pyruvate carboxylation. J Cereb Blood Flow Metab. 2000;20:327–336. doi: 10.1097/00004647-200002000-00014. PubMed DOI
Jitrapakdee S, St Maurice M, Rayment I, Wallace Cleland W, Wallace JC, Attwood PV. Structure, mechanism and regulation of pyruvate carboxylase. Biochem J. 2008;413:369–387. doi: 10.1042/BJ20080709. PubMed DOI PMC
Cappel DA, Deja S, Duarte JAG, Kucejova B, Iñigo M, Fletcher JA, Fu X, et al. Pyruvate-carboxylase-mediated anaplerosis promotes antioxidant capacity by sustaining TCA cycle and redox metabolism in liver. Cell Metab. 2019;29:1291–1305.e8. doi: 10.1016/j.cmet.2019.03.014. PubMed DOI PMC
Martínez-Reyes I, Chandel NS. Mitochondrial TCA cycle metabolites control physiology and disease. Nat Commun. 2020;11:102. doi: 10.1038/s41467-019-13668-3. PubMed DOI PMC
Martin-Requero A, Ayuso MS, Parrilla R. Interaction of oxamate with the gluconeogenic pathway in rat liver. Arch Biochem Biophys. 1986;246:114–127. doi: 10.1016/0003-9861(86)90455-8. PubMed DOI
Zhai X, Yang Y, Wan J, Zhu J, Wu Y. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep. 2013;30:2983–2991. doi: 10.3892/or.2013.2735. PubMed DOI
Thornburg JM, Nelson KK, Clem BF, Lane AN, Arumugam S, Simmons A, Eaton JW, Telang S, Chesney J. Targeting aspartate aminotransferase in breast cancer. Breast Cancer Res. 2008;10:R84. doi: 10.1186/bcr2154. PubMed DOI PMC
Oz G, Berkich DA, Henry P-G, Xu C, LaNoue K, Hutson SM, Gruetter R. Neuroglial metabolism in the awake rat brain: CO2 fixation increases with brain activity. J Neurosci. 2004;24:11273–11279. doi: 10.1523/JNEUROSCI.3564-04.2004. PubMed DOI PMC
Andersen JV, Markussen KH, Jakobsen E, Schousboe A, Waagepetersen HS, Rosenberg PA, Aldana BI. Glutamate metabolism and recycling at the excitatory synapse in health and neurodegeneration. Neuropharmacology. 2021;196:108719. doi: 10.1016/j.neuropharm.2021.108719. PubMed DOI
Andersen JV, Christensen SK, Westi EW, Diaz-delCastillo M, Tanila H, Schousboe A, Aldana BI, Waagepetersen HS. Deficient astrocyte metabolism impairs glutamine synthesis and neurotransmitter homeostasis in a mouse model of Alzheimer’s disease. Neurobiol Dis. 2021;148:105198. doi: 10.1016/j.nbd.2020.105198. PubMed DOI
Barber CN, Raben DM. Lipid metabolism crosstalk in the brain: glia and neurons. Front Cell Neurosci. 2019;13:212. doi: 10.3389/fncel.2019.00212. PubMed DOI PMC
Zhang J, Liu Q. Cholesterol metabolism and homeostasis in the brain. Protein Cell. 2015;6:254–264. doi: 10.1007/s13238-014-0131-3. PubMed DOI PMC
Jin U, Park SJ, Park SM. Cholesterol metabolism in the brain and its association with Parkinson’s disease. Exp Neurobiol. 2019;28:554–567. doi: 10.5607/en.2019.28.5.554. PubMed DOI PMC
Dietschy JM, Turley SD. Cholesterol metabolism in the brain. Curr Opin Lipidol. 2001;12:105–112. doi: 10.1097/00041433-200104000-00003. PubMed DOI
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