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Pregled bibliografske jedinice broj: 714474

Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis


Jazvinšćak Jembrek, Maja; Vlainić, Josipa; Radovanović, Vedrana; Erhardt, Julija; Oršolić, Nada
Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis // BioMetals, 27 (2014), 6; 1303-1322 doi:10.1007/s10534-014-9792-x (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 714474 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis

Autori
Jazvinšćak Jembrek, Maja ; Vlainić, Josipa ; Radovanović, Vedrana ; Erhardt, Julija ; Oršolić, Nada

Izvornik
BioMetals (0966-0844) 27 (2014), 6; 1303-1322

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Copper toxicity; P19 neurons; Glutathione; Lactate dehydrogenase; Apoptosis; Calpain; ERK pathway

Sažetak
Copper, a transition metal with essential biological functions, exerts neurotoxic effects when present in excess. The aim of the present study was to better elucidate cellular and molecular mechanisms of CuSO4 toxicity in differentiated P19 neurons. Exposure to 0.5 mM CuSO4 for 24 h provoked moderate decrease in viability, accompanied with barely increased generation of reactive oxygen species (ROS) and caspase-3/7 activity. Glutathione (GSH) and ATP contents were depleted, lactate dehydrogenase inactivated, and glyceraldehyde-3-phosphate dehydrogenase overexpressed. In severely damaged neurons exposed to only two times higher concentration, classical caspase-dependent apoptosis was triggered as evidenced by marked caspase-3/7 activation and chromatin condensation. Multifold increase in ROS, together with very pronounced ATP and GSH loss, strongly suggests impairment of redox homeostasis. At higher copper concentration protease calpains were also activated, and neuronal injury was prevented in the presence of calpain inhibitor leupeptin through the mechanism that affects caspase activation. MK-801 and nifedipine, inhibitors of calcium entry, and H-89 and UO126, inhibitors of PKA and ERK signaling respectively, exacerbated neuronal death only in severely damaged neurons, while ROS-scavenger quercetin and calcium chelator BAPTA attenuated toxicity only at lower concentration. In a dose-dependent manner copper also provoked transcriptional changes of genes involved in intracellular signaling and induction of apoptosis (p53, c-fos, Bcl-2 and Bax). The obtained results emphasize differences in triggered neuronal-death processes in a very narrow range of concentrations and give further insight into the molecular mechanisms of copper toxicity with the potential to improve current therapeutic approaches in curing copper-related neurodegenerative diseases.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti



POVEZANOST RADA


Projekti:
098-0000000-2448 - Stres, GABA-A receptori i mehanizmi djelovanja neuropsihofarmaka (Švob Štrac, Dubravka, MZOS ) ( POIROT)

Ustanove:
Institut "Ruđer Bošković", Zagreb,
Prirodoslovno-matematički fakultet, Zagreb,
Hrvatsko katoličko sveučilište, Zagreb

Poveznice na cjeloviti tekst rada:

doi link.springer.com

Citiraj ovu publikaciju:

Jazvinšćak Jembrek, Maja; Vlainić, Josipa; Radovanović, Vedrana; Erhardt, Julija; Oršolić, Nada
Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis // BioMetals, 27 (2014), 6; 1303-1322 doi:10.1007/s10534-014-9792-x (međunarodna recenzija, članak, znanstveni)
Jazvinšćak Jembrek, M., Vlainić, J., Radovanović, V., Erhardt, J. & Oršolić, N. (2014) Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis. BioMetals, 27 (6), 1303-1322 doi:10.1007/s10534-014-9792-x.
@article{article, author = {Jazvin\v{s}\'{c}ak Jembrek, Maja and Vlaini\'{c}, Josipa and Radovanovi\'{c}, Vedrana and Erhardt, Julija and Or\v{s}oli\'{c}, Nada}, year = {2014}, pages = {1303-1322}, DOI = {10.1007/s10534-014-9792-x}, keywords = {Copper toxicity, P19 neurons, Glutathione, Lactate dehydrogenase, Apoptosis, Calpain, ERK pathway}, journal = {BioMetals}, doi = {10.1007/s10534-014-9792-x}, volume = {27}, number = {6}, issn = {0966-0844}, title = {Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis}, keyword = {Copper toxicity, P19 neurons, Glutathione, Lactate dehydrogenase, Apoptosis, Calpain, ERK pathway} }
@article{article, author = {Jazvin\v{s}\'{c}ak Jembrek, Maja and Vlaini\'{c}, Josipa and Radovanovi\'{c}, Vedrana and Erhardt, Julija and Or\v{s}oli\'{c}, Nada}, year = {2014}, pages = {1303-1322}, DOI = {10.1007/s10534-014-9792-x}, keywords = {Copper toxicity, P19 neurons, Glutathione, Lactate dehydrogenase, Apoptosis, Calpain, ERK pathway}, journal = {BioMetals}, doi = {10.1007/s10534-014-9792-x}, volume = {27}, number = {6}, issn = {0966-0844}, title = {Effects of copper overload in P19 neurons : impairment of glutathione redox homeostasis and crosstalk between caspase and calpain protease systems in ROS-induced apoptosis}, keyword = {Copper toxicity, P19 neurons, Glutathione, Lactate dehydrogenase, Apoptosis, Calpain, ERK pathway} }

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


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