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Adenosine inhibits human astrocyte proliferation independently of adenosine receptor activation

2019Journal article Open access
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dc.contributor.authorMarcelino, Helena
dc.contributor.authorNogueira, Vanda Cristina Simões
dc.contributor.authorSantos, Cecilia
dc.contributor.authorQuelhas, Patricia
dc.contributor.authorCarvalho, Tiago
dc.contributor.authorGomes, João Fonseca
dc.contributor.authorTomás, Joana
dc.contributor.authorDiógenes, Maria José
dc.contributor.authorSebastião, Ana M
dc.contributor.authorCascalheira, José
dc.date.accessioned2019-12-20T16:15:52Z
dc.date.available2019-12-20T16:15:52Z
dc.date.issued2019
dc.description.abstractBrain adenosine concentrations can reach micromolar concentrations in stressful situations such as stroke, neurodegenerative diseases or hypoxic regions of brain tumours. Adenosine can act by receptor-independent mechanism by reversing the reaction catalysed by S-adenosylhomocysteine (SAH) hydrolase, leading to SAH accumulation and inhibition of S-adenosylmethionine (SAM)-dependent methyltransferases. Astrocytes are essential in maintaining brain homeostasis but their pathological activation and uncontrolled proliferation plays a role in neurodegeneration and glioma. Adenosine can affect cell proliferation, but the effect of increased adenosine concentration on proliferation of astrocytes is not clarified and was addressed in present work. Human astrocytes (HA) were treated for 3 days with test drugs. Cell proliferation/viability was assessed by the MTT assay and by cell counting. Cell death was evaluated by assessing lactate dehydrogenase (LDH) release and by western blot analysis of αII-Spectrin cleavage. 30µM-Adenosine caused a 40%±3% (p < .05, n = 5) reduction in cell proliferation/viability, an effect reversed by 2U/ml-adenosine deaminase, but unchanged in the presence of antagonists of any of the adenosine receptors. Adenosine alone did not induce cell death. 100µM-Homocysteine alone caused 16%±3% (p < .05) decrease in HA proliferation. Combined action of adenosine and homocysteine decreased HA proliferation by 76%±4%, an effect higher (p < .05) than the sum of the effect of adenosine and homocysteine alone (56%±5%). The inhibitory effect of adenosine on HA proliferation/viability was mimicked by two adenosine kinase inhibitors and attenuated in the presence of folate (100µM) or SAM (50-100µM). The results suggest that adenosine reduces HA proliferation by a receptor-independent mechanism probably involving reversal of SAH hydrolase-catalysed reaction.pt_PT
dc.description.versioninfo:eu-repo/semantics/acceptedVersionpt_PT
dc.identifier.doi10.1111/jnc.14937pt_PT
dc.identifier.urihttp://hdl.handle.net/10400.6/8002
dc.language.isoengpt_PT
dc.peerreviewednopt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectAdenosinept_PT
dc.subjectHuman astrocytespt_PT
dc.subjectMethyl group metabolismpt_PT
dc.subjectHomocysteinept_PT
dc.subjectSAMdependent methyltransferasespt_PT
dc.titleAdenosine inhibits human astrocyte proliferation independently of adenosine receptor activationpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/9471 - RIDTI/PTDC%2FBIM-ONC%2F7121%2F2014/PT
oaire.citation.startPagee14937pt_PT
oaire.citation.titleJournal of Neurochemistrypt_PT
oaire.fundingStream9471 - RIDTI
person.familyNameMarcelino
person.familyNameSANTOS
person.familyNameSilveira Quelhas
person.familyNameCarvalho
person.familyNameFonseca-Gomes
person.familyNameMelfe Tomás
person.familyNameDiógenes
person.familyNameSebastião
person.familyNameda Silva Cascalheira
person.givenNameHelena
person.givenNameCecília Reis Alves
person.givenNamePatrícia Alexandra
person.givenNameTiago
person.givenNameJoão
person.givenNameJoana Filipa
person.givenNameMaria José
person.givenNameAna M
person.givenNameJosé Francisco
person.identifier.ciencia-idF812-63AE-07C6
person.identifier.ciencia-id761A-7ED2-D68F
person.identifier.ciencia-id2316-8C6B-1212
person.identifier.ciencia-idAB1D-5817-12E1
person.identifier.ciencia-idA217-D5D0-E9BF
person.identifier.ciencia-idF51D-5365-D95D
person.identifier.ciencia-id4B10-886B-DAFC
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-idB219-078D-FD06
person.identifier.orcid0000-0002-6218-6192
person.identifier.orcid0000-0001-6074-7825
person.identifier.orcid0000-0001-8131-3081
person.identifier.orcid0000-0001-9095-1413
person.identifier.orcid0000-0001-7915-3517
person.identifier.orcid0000-0001-8796-5152
person.identifier.orcid0000-0001-5486-6246
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0002-5315-3866
person.identifier.ridE-7661-2015
person.identifier.scopus-author-id35080864400
person.identifier.scopus-author-id36818952300
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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