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Sökning: (AMNE:(Neurovetenskaper)) srt2:(2005-2009) > (2007) > Changes in calcium ...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00003733naa a2200493 4500
001oai:lup.lub.lu.se:264f2250-3070-4be1-be71-16eb7455dee2
003SwePub
008160401s2007 | |||||||||||000 ||eng|
024a https://lup.lub.lu.se/record/6927932 URI
024a https://doi.org/10.1038/sj.cdd.44021712 DOI
040 a (SwePub)lu
041 a engb eng
042 9 SwePub
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
100a Araujo, I. M.4 aut
2451 0a Changes in calcium dynamics following the reversal of the sodium-calcium exchanger have a key role in AMPA receptor-mediated neurodegeneration via calpain activation in hippocampal neurons
264 c 2007-06-22
264 1b Springer Science and Business Media LLC,c 2007
520 a Proteolytic cleavage of the Na+/Ca2+ exchanger (NCX) by calpains impairs calcium homeostasis, leading to a delayed calcium overload and excitotoxic cell death. However, it is not known whether reversal of the exchanger contributes to activate calpains and trigger neuronal death. We investigated the role of the reversal of the NCX in Ca2+ dynamics, calpain activation and cell viability, in alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptor-stimulated hippocampal neurons. Selective overactivation of AMPA receptors caused the reversal of the NCX, which accounted for approximately 30% of the rise in intracellular free calcium concentration ([Ca2+](i)). The NCX reverse-mode inhibitor, 2-[2-[4-(4-nitrobenzyloxy) phenyl]ethyl] isothiourea (KB-R7943), partially inhibited the initial increase in [Ca2+](i), and prevented a delayed increase in [Ca2+](i). In parallel, overactivation of AMPA receptors strongly activated calpains and led to the proteolysis of NCX3. KB-R7943 prevented calpain activation, cleavage of NCX3 and was neuroprotective. Silencing of NCX3 reduced Ca2+ uptake, calpain activation and was neuroprotective. Our data show for the first time that NCX reversal is an early event following AMPA receptor stimulation and is linked to the activation of calpains. Since calpain activation subsequently inactivates NCX, causing a secondary Ca2+ entry, NCX may be viewed as a new suicide substrate operating in a Ca2+-dependent loop that triggers cell death and as a target for neuroprotection.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinska och farmaceutiska grundvetenskaperx Neurovetenskaper0 (SwePub)301052 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Basic Medicinex Neurosciences0 (SwePub)301052 hsv//eng
653 a sodium-calcium
653 a proteolysis
653 a calpains
653 a excitotoxicity
653 a calcium
653 a AMPA receptors
653 a exchanger
700a Carreira, B. P.4 aut
700a Pereira, T.4 aut
700a Santos, P. F.4 aut
700a Soulet, Denisu Lund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine4 aut0 (Swepub:lu)med-des
700a Inacio, A.4 aut
700a Bahr, B. A.4 aut
700a Carvalho, A. P.4 aut
700a Ambrosio, A. F.4 aut
700a Carvalho, C. M.4 aut
710a Institutionen för experimentell medicinsk vetenskapb Medicinska fakulteten4 org
773t Cell Death and Differentiationd : Springer Science and Business Media LLCg 14:9, s. 1635-1646q 14:9<1635-1646x 1350-9047x 1476-5403
856u http://dx.doi.org/10.1038/sj.cdd.4402171y FULLTEXT
856u https://www.nature.com/articles/4402171.pdf
8564 8u https://lup.lub.lu.se/record/692793
8564 8u https://doi.org/10.1038/sj.cdd.4402171

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