Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone
Joint Authors
Cuenca-Lopez, Maria D.
Kmita, Hanna
Jordán Bueso, Joaquín
Villalobos, Carlos
Galindo, Maria F.
Perez-Alvarez, Sergio
Solesio, Maria E.
Melero-Fernández de Mera, Raquel M.
Source
International Journal of Cell Biology
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-06-17
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Previously, we have shown that SH-SY5Y cells exposed to high concentrations of methadone died due to a necrotic-like cell death mechanism related to delayed calcium deregulation (DCD).
In this study, we show that, in terms of their Ca2+ responses to 0.5 mM methadone, SH-SY5Y cells can be pooled into four different groups.
In a broad pharmacological survey, the relevance of different Ca2+-related mechanisms on methadone-induced DCD was investigated including extracellular calcium, L-type Ca2+ channels, μ-opioid receptor, mitochondrial inner membrane potential, mitochondrial ATP synthesis, mitochondrial Ca2+/2Na+-exchanger, reactive oxygen species, and mitochondrial permeability transition.
Only those compounds targeting mitochondria such as oligomycin, FCCP, CGP 37157, and cyclosporine A were able to amend methadone-induced Ca2+ dyshomeostasis suggesting that methadone induces DCD by modulating the ability of mitochondria to handle Ca2+.
Consistently, mitochondria became dramatically shorter and rounder in the presence of methadone.
Furthermore, analysis of oxygen uptake by isolated rat liver mitochondria suggested that methadone affected mitochondrial Ca2+ uptake in a respiratory substrate-dependent way.
We conclude that methadone causes failure of intracellular Ca2+ homeostasis, and this effect is associated with morphological and functional changes of mitochondria.
Likely, this mechanism contributes to degenerative side effects associated with methadone treatment.
American Psychological Association (APA)
Perez-Alvarez, Sergio& Solesio, Maria E.& Cuenca-Lopez, Maria D.& Melero-Fernández de Mera, Raquel M.& Villalobos, Carlos& Kmita, Hanna…[et al.]. 2012. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone. International Journal of Cell Biology،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-487599
Modern Language Association (MLA)
Perez-Alvarez, Sergio…[et al.]. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone. International Journal of Cell Biology No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-487599
American Medical Association (AMA)
Perez-Alvarez, Sergio& Solesio, Maria E.& Cuenca-Lopez, Maria D.& Melero-Fernández de Mera, Raquel M.& Villalobos, Carlos& Kmita, Hanna…[et al.]. Pharmacological Characterization of the Mechanisms Involved in Delayed Calcium Deregulation in SH-SY5Y Cells Challenged with Methadone. International Journal of Cell Biology. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-487599
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-487599