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Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds

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Abstract

In this review, we show how chromaffin cells have contributed to evaluate neuroprotective compounds with diverse mechanisms of action. Chromaffin cells are considered paraneurons, as they share many common features with neurons: (i) they synthesize, store, and release neurotransmitters upon stimulation and (ii) they express voltage-dependent calcium, sodium, and potassium channels, in addition to a wide variety of receptors. All these characteristics, together with the fact that primary cultures from bovine adrenal glands or chromaffin cells from the tumor pheochromocytoma cell line PC12 are easy to culture, make them an ideal model to study neurotoxic mechanisms and neuroprotective drugs. In the first part of this review, we will analyze the different cytotoxicity models related to calcium dyshomeostasis and neurodegenerative disorders like Alzheimer’s or Parkinson’s. Along the second part of the review, we describe how different classes of drugs have been evaluated in chromaffin cells to determine their neuroprotective profile in different neurodegenerative-related models.

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References

  1. Douglas WW, Rubin RP (1961) The role of calcium in the secretory response of the adrenal medulla to acetylcholine. J Physiol 159:40–57

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Wilson SP, Kirshner N (1977) The acetylcholine receptor of the adrenal medulla. J Neurochem 28:687–695

    Article  CAS  PubMed  Google Scholar 

  3. Douglas WW, Poisner AM (1965) Preferential release of adrenaline from the adrenal medulla by muscarine and pilocarpine. Nature 208:1102–1103

    Article  CAS  PubMed  Google Scholar 

  4. Artalejo AR, Garcia AG, Neher E (1993) Small-conductance Ca(2+)-activated K+ channels in bovine chromaffin cells. Pflugers Arch 423:97–103

    Article  CAS  PubMed  Google Scholar 

  5. Fenwick EM, Marty A, Neher E (1982) Sodium and calcium channels in bovine chromaffin cells. J Physiol 331:599–635

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Garcia AG, Garcia-De-Diego AM, Gandia L, Borges R, Garcia-Sancho J (2006) Calcium signaling and exocytosis in adrenal chromaffin cells. Physiol Rev 86:1093–1131. doi:10.1152/physrev.00039.2005

    Article  CAS  PubMed  Google Scholar 

  7. Kidokoro Y, Ritchie AK (1980) Chromaffin cell action potentials and their possible role in adrenaline secretion from rat adrenal medulla. J Physiol 307:199–216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Uceda G, Colombo JA, Michelena P, Lopez MG, Garcia AG (1995) Rat striatal astroglia induce morphological and neurochemical changes in adult bovine, adrenergic-enriched adrenal chromaffin cells in vitro. Restor Neurol Neurosci 8:129–136. doi:10.3233/RNN-1995-8303

    CAS  PubMed  Google Scholar 

  9. Unsicker K, Rieffert B, Ziegler W (1980) Effects of cell culture conditions, nerve growth factor, dexamethasone, and cyclic AMP on adrenal chromaffin cells in vitro. Adv Biochem Psychopharmacol 25:51–59

    CAS  PubMed  Google Scholar 

  10. Campan L (1978) A missed opportunity in anesthesiology: Claude Bernard. Ann Anesthesiol Fr 19:3–6

    CAS  PubMed  Google Scholar 

  11. Moro MA, Lopez MG, Gandia L, Michelena P, Garcia AG (1990) Separation and culture of living adrenaline- and noradrenaline-containing cells from bovine adrenal medullae. Anal Biochem 185:243–248

    Article  CAS  PubMed  Google Scholar 

  12. Cano-Abad MF, Villarroya M, Garcia AG, Gabilan NH, Lopez MG (2001) Calcium entry through L-type calcium channels causes mitochondrial disruption and chromaffin cell death. J Biol Chem 276:39695–39704. doi:10.1074/jbc.M102334200

    Article  CAS  PubMed  Google Scholar 

  13. Albillos A, Garcia AG, Olivera B, Gandia L (1996) Re-evaluation of the P/Q Ca2+ channel components of Ba2+ currents in bovine chromaffin cells superfused with solutions containing low and high Ba2+ concentrations. Pflugers Arch 432:1030–1038

    Article  CAS  PubMed  Google Scholar 

  14. Ota M, Narahashi T, Keeler RF (1973) Effects of veratrum alkaloids on membrane potential and conductance of squid and crayfish giant axons. J Pharmacol Exp Ther 184:143–154

    CAS  PubMed  Google Scholar 

  15. Lopez MG, Artalejo AR, Garcia AG, Neher E, Garcia-Sancho J (1995) Veratridine-induced oscillations of cytosolic calcium and membrane potential in bovine chromaffin cells. J Physiol 482(Pt 1):15–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Cano-Abad MF, Lopez MG, Hernandez-Guijo JM, Zapater P, Gandia L, Sanchez-Garcia P, Garcia AG (1998) Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells. Br J Pharmacol 124:1187–1196. doi:10.1038/sj.bjp.0701955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Jordan J, Galindo MF, Calvo S, Gonzalez-Garcia C, Cena V (2000) Veratridine induces apoptotic death in bovine chromaffin cells through superoxide production. Br J Pharmacol 130:1496–1504. doi:10.1038/sj.bjp.0703451

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Jordan J, Galindo MF, Tornero D, Benavides A, Gonzalez C, Agapito MT, Gonzalez-Garcia C, Cena V (2002) Superoxide anions mediate veratridine-induced cytochrome c release and caspase activity in bovine chromaffin cells. Br J Pharmacol 137:993–1000. doi:10.1038/sj.bjp.0704953

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Shimoke K, Chiba H (2001) Nerve growth factor prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced cell death via the Akt pathway by suppressing caspase-3-like activity using PC12 cells: relevance to therapeutical application for Parkinson’s disease. J Neurosci Res 63:402–409. doi:10.1002/1097-4547(20010301)63:5<402::AID-JNR1035>3.0.CO;2-F

    Article  CAS  PubMed  Google Scholar 

  20. Guo Q, Sopher BL, Furukawa K, Pham DG, Robinson N, Martin GM, Mattson MP (1997) Alzheimer’s presenilin mutation sensitizes neural cells to apoptosis induced by trophic factor withdrawal and amyloid beta-peptide: involvement of calcium and oxyradicals. J Neurosci 17:4212–4222

    CAS  PubMed  Google Scholar 

  21. Akhter R, Sanphui P, Biswas SC (2014) The essential role of p53-up-regulated modulator of apoptosis (PUMA) and its regulation by FoxO3a transcription factor in beta-amyloid-induced neuron death. J Biol Chem 289:10812–10822. doi:10.1074/jbc.M113.519355

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Sanphui P, Biswas SC (2013) FoxO3a is activated and executes neuron death via Bim in response to beta-amyloid. Cell Death Dis 4:e625. doi:10.1038/cddis.2013.148

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Fukuyama R, Wadhwani KC, Galdzicki Z, Rapoport SI, Ehrenstein G (1994) Beta-amyloid polypeptide increases calcium-uptake in PC12 cells: a possible mechanism for its cellular toxicity in Alzheimer’s disease. Brain Res 667:269–272

    Article  CAS  PubMed  Google Scholar 

  24. Greenberg SM, Koo EH, Selkoe DJ, Qiu WQ, Kosik KS (1994) Secreted beta-amyloid precursor protein stimulates mitogen-activated protein kinase and enhances tau phosphorylation. Proc Natl Acad Sci U S A 91:7104–7108

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Andrew R, Watson DG, Best SA, Midgley JM, Wenlong H, Petty RK (1993) The determination of hydroxydopamines and other trace amines in the urine of Parkinsonian patients and normal controls. Neurochem Res 18:1175–1177

    Article  CAS  PubMed  Google Scholar 

  26. Ljungdahl A, Hokfelt T, Jonsson G, Sachs C (1971) Autoradiographic demonstration of uptake and accumulation of 3H-6-hydroxydopamine in adrenergic nerves. Experientia 27:297–299

    Article  CAS  PubMed  Google Scholar 

  27. Blum D, Torch S, Lambeng N, Nissou M, Benabid AL, Sadoul R, Verna JM (2001) Molecular pathways involved in the neurotoxicity of 6-OHDA, dopamine and MPTP: contribution to the apoptotic theory in Parkinson’s disease. Prog Neurobiol 65:135–172

    Article  CAS  PubMed  Google Scholar 

  28. Blum D, Torch S, Nissou MF, Benabid AL, Verna JM (2000) Extracellular toxicity of 6-hydroxydopamine on PC12 cells. Neurosci Lett 283:193–196

    Article  CAS  PubMed  Google Scholar 

  29. Soto-Otero R, Mendez-Alvarez E, Hermida-Ameijeiras A, Munoz-Patino AM, Labandeira-Garcia JL (2000) Autoxidation and neurotoxicity of 6-hydroxydopamine in the presence of some antioxidants: potential implication in relation to the pathogenesis of Parkinson’s disease. J Neurochem 74:1605–1612

    Article  CAS  PubMed  Google Scholar 

  30. Hanrott K, Gudmunsen L, O’Neill MJ, Wonnacott S (2006) 6-hydroxydopamine-induced apoptosis is mediated via extracellular auto-oxidation and caspase 3-dependent activation of protein kinase Cdelta. J Biol Chem 281:5373–5382. doi:10.1074/jbc.M511560200

    Article  CAS  PubMed  Google Scholar 

  31. Saito Y, Nishio K, Ogawa Y, Kinumi T, Yoshida Y, Masuo Y, Niki E (2007) Molecular mechanisms of 6-hydroxydopamine-induced cytotoxicity in PC12 cells: involvement of hydrogen peroxide-dependent and -independent action. Free Radic Biol Med 42:675–685. doi:10.1016/j.freeradbiomed.2006.12.004

    Article  CAS  PubMed  Google Scholar 

  32. Lee DH, Han YS, Han ES, Bang H, Lee CS (2006) Differential involvement of intracellular Ca2+ in 1-methyl-4-phenylpyridinium- or 6-hydroxydopamine-induced cell viability loss in PC12 cells. Neurochem Res 31:851–860. doi:10.1007/s11064-006-9088-9

    Article  CAS  PubMed  Google Scholar 

  33. Liu C, Ye Y, Zhou Q, Zhang R, Zhang H, Liu W, Xu C, Liu L, Huang S, Chen L (2016) Crosstalk between Ca2+ signaling and mitochondrial H2O2 is required for rotenone inhibition of mTOR signaling pathway leading to neuronal apoptosis. Oncotarget 7:7534–7549. doi:10.18632/oncotarget.7183

    Article  PubMed  PubMed Central  Google Scholar 

  34. Arias E, Ales E, Gabilan NH, Cano-Abad MF, Villarroya M, Garcia AG, Lopez MG (2004) Galantamine prevents apoptosis induced by beta-amyloid and thapsigargin: involvement of nicotinic acetylcholine receptors. Neuropharmacology 46:103–114

    Article  CAS  PubMed  Google Scholar 

  35. Leon R, Marco-Contelles J, Garcia AG, Villarroya M (2005) Synthesis, acetylcholinesterase inhibition and neuroprotective activity of new tacrine analogues. Bioorg Med Chem 13:1167–1175. doi:10.1016/j.bmc.2004.11.020

    Article  CAS  PubMed  Google Scholar 

  36. Marco-Contelles J, Leon R, Lopez MG, Garcia AG, Villarroya M (2006) Synthesis and biological evaluation of new 4H-pyrano[2,3-b]quinoline derivatives that block acetylcholinesterase and cell calcium signals, and cause neuroprotection against calcium overload and free radicals. Eur J Med Chem 41:1464–1469. doi:10.1016/j.ejmech.2006.06.016

    Article  CAS  PubMed  Google Scholar 

  37. Egea J, Rosa AO, Cuadrado A, Garcia AG, Lopez MG (2007) Nicotinic receptor activation by epibatidine induces heme oxygenase-1 and protects chromaffin cells against oxidative stress. J Neurochem 102:1842–1852. doi:10.1111/j.1471-4159.2007.04665.x

    Article  CAS  PubMed  Google Scholar 

  38. Yokoo H, Shiraishi S, Kobayashi H, Yanagita T, Minami S, Yamamoto R, Wada A (2000) Inhibition by neuroprotective drug NS-7 of nicotine-induced 22Na(+) influx, 45Ca(2+) influx and catecholamine secretion in adrenal chromaffin cells. Brain Res 873:149–154

    Article  CAS  PubMed  Google Scholar 

  39. Yokoo H, Shiraishi S, Kobayashi H, Yanagita T, Minami S, Yamamoto R, Wada A (2000) Short- and long-term differential effects of neuroprotective drug NS-7 on voltage-dependent sodium channels in adrenal chromaffin cells. Br J Pharmacol 131:779–787. doi:10.1038/sj.bjp.0703622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Valero T, del Barrio L, Egea J, Canas N, Martinez A, Garcia AG, Villarroya M, Lopez MG (2009) NP04634 prevents cell damage caused by calcium overload and mitochondrial disruption in bovine chromaffin cells. Eur J Pharmacol 607:47–53. doi:10.1016/j.ejphar.2009.02.021

    Article  CAS  PubMed  Google Scholar 

  41. Abad F, Maroto R, Lopez MG, Sanchez-Garcia P, Garcia AG (1995) Pharmacological protection against the cytotoxicity induced by 6-hydroxydopamine and H2O2 in chromaffin cells. Eur J Pharmacol 293:55–64

    Article  CAS  PubMed  Google Scholar 

  42. Cano-Abad MF, Garcia AG, Sanchez-Garcia P, Lopez MG (2000) Ba(2+)-induced chromaffin cell death: cytoprotection by Ca(2+) channel antagonists. Eur J Pharmacol 402:19–29

    Article  CAS  PubMed  Google Scholar 

  43. Young LM, Geldenhuys WJ, Domingo OC, Malan SF, Van der Schyf CJ (2016) Synthesis and biological evaluation of pentacycloundecylamines and triquinylamines as voltage-gated calcium channel blockers. Arch Pharm (Weinheim) 349:252–267. doi:10.1002/ardp.201500293

    Article  CAS  Google Scholar 

  44. Novalbos J, Abad-Santos F, Zapater P, Alvarez J, Alonso MT, Montero M, Garcia AG (1999) Novel antimigraineur dotarizine releases Ca2+ from caffeine-sensitive Ca2+ stores of chromaffin cells. Br J Pharmacol 128:621–626. doi:10.1038/sj.bjp.0702853

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Novalbos J, Abad-Santos F, Zapater P, Cano-Abad MF, Moradiellos J, Sanchez-Garcia P, Garcia AG (1999) Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+. Eur J Pharmacol 366:309–317

    Article  CAS  PubMed  Google Scholar 

  46. Martinez-Sanz FJ, Lajarin-Cuesta R, Gonzalez-Lafuente L, Moreno-Ortega AJ, Punzon E, Cano-Abad MF, de los Rios C (2016) Neuroprotective profile of pyridothiazepines with blocking activity of the mitochondrial Na(+)/Ca(2+) exchanger. Eur J Med Chem 109:114–123. doi:10.1016/j.ejmech.2015.12.043

    Article  CAS  PubMed  Google Scholar 

  47. Martinez-Sanz FJ, Lajarin-Cuesta R, Moreno-Ortega AJ, Gonzalez-Lafuente L, Fernandez-Morales JC, Lopez-Arribas R, Cano-Abad MF, de los Rios C (2015) Benzothiazepine CGP37157 analogues exert cytoprotection in various in vitro models of neurodegeneration. ACS Chem Neurosci 6:1626–1636. doi:10.1021/acschemneuro.5b00161

    Article  CAS  PubMed  Google Scholar 

  48. Nicolau SM, de Diego AM, Cortes L, Egea J, Gonzalez JC, Mosquera M, Lopez MG, Hernandez-Guijo JM, Garcia AG (2009) Mitochondrial Na+/Ca2+-exchanger blocker CGP37157 protects against chromaffin cell death elicited by veratridine. J Pharmacol Exp Ther 330:844–854. doi:10.1124/jpet.109.154765

    Article  CAS  PubMed  Google Scholar 

  49. Buendia I, Tenti G, Michalska P, Mendez-Lopez I, Luengo E, Satriani M, Padin-Nogueira F, Lopez MG, Ramos MT, Garcia AG, Menendez JC, Leon R (2017) ITH14001, a CGP37157-nimodipine hybrid designed to regulate calcium homeostasis and oxidative stress, exerts neuroprotection in cerebral ischemia. ACS Chem Neurosci 8:67–81. doi:10.1021/acschemneuro.6b00181

    Article  CAS  PubMed  Google Scholar 

  50. Wood PL, Hawkinson JE (1997) N-methyl-D-aspartate antagonists for stroke and head trauma. Expert Opin Investig Drugs 6:389–397. doi:10.1517/13543784.6.4.389

    Article  CAS  PubMed  Google Scholar 

  51. Hernandez-Guijo JM, Gandia L, de Pascual R, Garcia AG (1997) Differential effects of the neuroprotectant lubeluzole on bovine and mouse chromaffin cell calcium channel subtypes. Br J Pharmacol 122:275–285. doi:10.1038/sj.bjp.0701364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Maroto R, De la Fuente MT, Artalejo AR, Abad F, Lopez MG, Garcia-Sancho J, Garcia AG (1994) Effects of Ca2+ channel antagonists on chromaffin cell death and cytosolic Ca2+ oscillations induced by veratridine. Eur J Pharmacol 270:331–339

    CAS  PubMed  Google Scholar 

  53. Chiesi M, Schwaller R, Eichenberger K (1988) Structural dependency of the inhibitory action of benzodiazepines and related compounds on the mitochondrial Na+-Ca2+ exchanger. Biochem Pharmacol 37:4399–4403

    Article  CAS  PubMed  Google Scholar 

  54. Czyz A, Kiedrowski L (2003) Inhibition of plasmalemmal Na(+)/Ca(2+) exchange by mitochondrial Na(+)/Ca(2+) exchange inhibitor 7-chloro-5-(2-chlorophenyl)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP-37157) in cerebellar granule cells. Biochem Pharmacol 66:2409–2411

    Article  CAS  PubMed  Google Scholar 

  55. Moreno-Ortega AJ, Martinez-Sanz FJ, Lajarin-Cuesta R, de Los RC, Cano-Abad MF (2015) Benzothiazepine CGP37157 and its 2′-isopropyl analogue modulate Ca(2)(+) entry through CALHM1. Neuropharmacology 95:503–510. doi:10.1016/j.neuropharm.2015.02.016

    Article  CAS  PubMed  Google Scholar 

  56. Lopez-Gil A, Nanclares C, Mendez-Lopez I, Martinez-Ramirez C, de Los RC, Padin-Nogueira JF, Montero M, Gandia L, Garcia AG (2017) The quantal catecholamine release from mouse chromaffin cells challenged with repeated ACh pulses is regulated by the mitochondrial Na+/Ca2+ exchanger. J Physiol 595:2129–2146. doi:10.1113/JP273339

    Article  CAS  PubMed  Google Scholar 

  57. Corona-Morales AA, Castell A, Escobar A, Drucker-Colin R, Zhang L (2003) Fullerene C60 and ascorbic acid protect cultured chromaffin cells against levodopa toxicity. J Neurosci Res 71:121–126. doi:10.1002/jnr.10456

    Article  CAS  PubMed  Google Scholar 

  58. Wang L, Wang R, Jin M, Huang Y, Liu A, Qin J, Chen M, Wen S, Pi R, Shen W (2014) Carvedilol attenuates 6-hydroxydopamine-induced cell death in PC12 cells: involvement of Akt and Nrf2/ARE pathways. Neurochem Res 39:1733–1740. doi:10.1007/s11064-014-1367-2

    Article  CAS  PubMed  Google Scholar 

  59. Jiang BP, Le L, Xu LJ, Xiao PG (2014) Minocycline inhibits ICAD degradation and the NF-kappaB activation induced by 6-OHDA in PC12 cells. Brain Res 1586:1–11. doi:10.1016/j.brainres.2014.08.001

    Article  CAS  PubMed  Google Scholar 

  60. Xu YQ, Long L, Yan JQ, Wei L, Pan MQ, Gao HM, Zhou P, Liu M, Zhu CS, Tang BS, Wang Q (2013) Simvastatin induces neuroprotection in 6-OHDA-lesioned PC12 via the PI3K/AKT/caspase 3 pathway and anti-inflammatory responses. CNS Neurosci Ther 19:170–177. doi:10.1111/cns.12053

    Article  PubMed  Google Scholar 

  61. Mayo JC, Sainz RM, Uria H, Antolin I, Esteban MM, Rodriguez C (1998) Melatonin prevents apoptosis induced by 6-hydroxydopamine in neuronal cells: implications for Parkinson’s disease. J Pineal Res 24:179–192

    Article  CAS  PubMed  Google Scholar 

  62. Takadera T, Yoshikawa R, Ohyashiki T (2006) Thapsigargin-induced apoptosis was prevented by glycogen synthase kinase-3 inhibitors in PC12 cells. Neurosci Lett 408:124–128. doi:10.1016/j.neulet.2006.08.066

    Article  CAS  PubMed  Google Scholar 

  63. Charalampopoulos I, Alexaki VI, Tsatsanis C, Minas V, Dermitzaki E, Lasaridis I, Vardouli L, Stournaras C, Margioris AN, Castanas E, Gravanis A (2006) Neurosteroids as endogenous inhibitors of neuronal cell apoptosis in aging. Ann N Y Acad Sci 1088:139–152. doi:10.1196/annals.1366.003

    Article  CAS  PubMed  Google Scholar 

  64. Orozco C, de Los RC, Arias E, Leon R, Garcia AG, Marco JL, Villarroya M, Lopez MG (2004) ITH4012 (ethyl 5-amino-6,7,8,9-tetrahydro-2-methyl-4-phenylbenzol[1,8]naphthyridine-3-carboxylat e), a novel acetylcholinesterase inhibitor with “calcium promotor” and neuroprotective properties. J Pharmacol Exp Ther 310:987–994. doi:10.1124/jpet.104.068189

    Article  CAS  PubMed  Google Scholar 

  65. Baulieu EE, Robel P (1998) Dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulfate (DHEAS) as neuroactive neurosteroids. Proc Natl Acad Sci U S A 95:4089–4091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Straub RH, Lehle K, Herfarth H, Weber M, Falk W, Preuner J, Scholmerich J (2002) Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor. Eur J Endocrinol 146:365–374

    Article  CAS  PubMed  Google Scholar 

  67. Wolkowitz OM, Epel ES, Reus VI (2001) Stress hormone-related psychopathology: pathophysiological and treatment implications. World J Biol Psychiatry 2:115–143

    Article  CAS  PubMed  Google Scholar 

  68. Weill-Engerer S, David JP, Sazdovitch V, Liere P, Eychenne B, Pianos A, Schumacher M, Delacourte A, Baulieu EE, Akwa Y (2002) Neurosteroid quantification in human brain regions: comparison between Alzheimer’s and nondemented patients. J Clin Endocrinol Metab 87:5138–5143. doi:10.1210/jc.2002-020878

    Article  CAS  PubMed  Google Scholar 

  69. Orozco C, Garcia-de-Diego AM, Arias E, Hernandez-Guijo JM, Garcia AG, Villarroya M, Lopez MG (2006) Depolarization preconditioning produces cytoprotection against veratridine-induced chromaffin cell death. Eur J Pharmacol 553:28–38. doi:10.1016/j.ejphar.2006.08.084

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We acknowledge the Spanish Ministry of Economy and Competence ref. SAF2015-63935R to MGL. We thank Instituto de Salud Carlos III (PI16/01041) for funding to CdlR. We also thank the Fundación Teófilo Hernando for its continuous support.

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Correspondence to Manuela G. López.

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This article is part of the special issue on Chromaffin Cells in Pflügers Archiv – European Journal of Physiology

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de los Rios, C., Cano-Abad, M.F., Villarroya, M. et al. Chromaffin cells as a model to evaluate mechanisms of cell death and neuroprotective compounds. Pflugers Arch - Eur J Physiol 470, 187–198 (2018). https://doi.org/10.1007/s00424-017-2044-5

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