Author | Vieira, Saulo Martins | |
Author | Oliveira, Vanessa Honorato de | |
Author | Valente, Raphael do Carmo | |
Author | Moreira, Otacílio da Cruz | |
Author | Fontes, Carlos Frederico Leite | |
Author | Mignaco, Julio Alberto | |
Access date | 2016-03-08T16:00:34Z | |
Available date | 2016-03-08T16:00:34Z | |
Document date | 2015 | |
Citation | VIEIRA, Saulo Martins; et al. Chelerythrine inhibits the sarco/endoplasmic reticulum Ca2+-ATPase and results in cell Ca2+ imbalance. Archives of Biochemistry and Biophysics, v.570, p.58-65, Mar. 2015. | pt_BR |
ISSN | 0003-9861 | |
URI | https://www.arca.fiocruz.br/handle/icict/13059 | |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | restricted access | |
Title | Chelerythrine inhibits the sarco/endoplasmic reticulum Ca2+-ATPase and results in cell Ca2+ imbalance | pt_BR |
Type | Article | |
DOI | 10.1016/j.abb.2015.02.019 | |
Abstract | The isoquinoline alkaloid chelerythrine is described as an inhibitor of SERCA. The ATPase inhibition presented two non-competitive components, Ki1 = 1, 2 μM and Ki2 = 26 μM. Conversely, chelerythrine presented a dual effect on the p-nitrophenylphosphatase (pNPPase) of SERCA. Ca2+-dependent pNPPase was activated up to ∼5 μM chelerythrine with inhibition thereafter. Ca2+-independent pNPPase was solely inhibited. The phosphorylation of SERCA with ATP reached half-inhibition with 10 μM chelerythrine and did not parallel the decrease of ATPase activity. In contrast, chelerythrine up to 50 μM increased the phosphorylation by Pi. Cross-linking of SERCA with glutaraldehyde was counteracted by high concentrations of chelerythrine. The controlled tryptic digestion of SERCA shows that the low-affinity binding of chelerythrine evoked an E2-like pattern. Our data indicate a non-competitive inhibition of ATP hydrolysis that favors buildup of the E2-conformers of the enzyme. Chelerythrine as low as 0.5–1.5 μM resulted in an increase of intracellular Ca2+ on cultured PBMC cells. The inhibition of SERCA and the loss of cell Ca2+ homeostasis could in part be responsible for some described cytotoxic effects of the alkaloid. Thus, the choice of chelerythrine as a PKC-inhibitor should consider its potential cytotoxicity due to the alkaloid’s effects on SERCA. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Biofísica Carlos Chagas Filho. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade Federal do Rio de Janeiro. Centro de Ciências da Saúde. Instituto de Bioquímica Médica Leopoldo de Meis. Rio de Janeiro, RJ, Brasil. | pt_BR |
Subject | SERCA | pt_BR |
Subject | ATPase | pt_BR |
Subject | Chelerythrine | pt_BR |
Subject | PBMC | pt_BR |
Subject | Cytotoxicity | pt_BR |
Subject | Calcium | pt_BR |
DeCS | Citotoxicidade | pt_BR |
DeCS | Cálcio | pt_BR |