Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal
Joint Authors
Zhang, Yiting
Waly, Mostafa
Power-Charnitsky, Verna-Ann
Sharma, Alok
Audhya, Tapan
Deth, Richard C.
Hodgson, Nathaniel
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2016, Issue 2016 (31 Dec. 2016), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2016-02-18
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
The folate and cobalamin (Cbl-) dependent enzyme methionine synthase (MS) is highly sensitive to oxidation and its activity affects all methylation reactions.
Recent studies have revealed alternative splicing of MS mRNA in human brain and patient-derived fibroblasts.
Here we show that MS mRNA in SH-SY5Y human neuroblastoma cells is alternatively spliced, resulting in three primary protein species, thus providing a useful model to examine cofactor dependence of these variant enzymes.
MS activity was dependent upon methylcobalamin (MeCbl) or the combination of hydroxocobalamin (OHCbl) and S-adenosylmethionine (SAM).
OHCbl-based activity was eliminated by depletion of the antioxidant glutathione (GSH) but could be rescued by provision of either glutathionylcobalamin (GSCbl) or MeCbl.
Pretreatment of cells with lead, arsenic, aluminum, mercury, or the ethylmercury-containing preservative thimerosal lowered GSH levels and inhibited MS activity in association with decreased uptake of cysteine, which is rate-limiting for GSH synthesis.
Thimerosal treatment decreased cellular levels of GSCbl and MeCbl.
These findings indicate that the alternatively spliced form of MS expressed in SH-SY5Y human neuronal cells is sensitive to inhibition by thimerosal and neurotoxic metals, and lower GSH levels contribute to their inhibitory action.
American Psychological Association (APA)
Waly, Mostafa& Power-Charnitsky, Verna-Ann& Hodgson, Nathaniel& Sharma, Alok& Audhya, Tapan& Zhang, Yiting…[et al.]. 2016. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal. Oxidative Medicine and Cellular Longevity،Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1114086
Modern Language Association (MLA)
Waly, Mostafa…[et al.]. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal. Oxidative Medicine and Cellular Longevity No. 2016 (2016), pp.1-11.
https://search.emarefa.net/detail/BIM-1114086
American Medical Association (AMA)
Waly, Mostafa& Power-Charnitsky, Verna-Ann& Hodgson, Nathaniel& Sharma, Alok& Audhya, Tapan& Zhang, Yiting…[et al.]. Alternatively Spliced Methionine Synthase in SH-SY5Y Neuroblastoma Cells: Cobalamin and GSH Dependence and Inhibitory Effects of Neurotoxic Metals and Thimerosal. Oxidative Medicine and Cellular Longevity. 2016. Vol. 2016, no. 2016, pp.1-11.
https://search.emarefa.net/detail/BIM-1114086
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1114086