Differential regulation of cell proliferation in neurogenic zones in mice lacking cystine transport by xCT

Journal Article · Fri Dec 21 00:00:00 EST 2007 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2007.10.036· OSTI ID:21033016

Liu, Richard R ^[1]; Brown, Craig E ^[1]; Murphy, Timothy H ^[1]

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1. Kinsmen Laboratory, Department of Psychiatry, University of British Columbia, 4N1-2255 Wesbrook Mall, Vancouver, BC, V6T 1Z3 (Canada)

The cystine/glutamate exchanger (xCT) supplies intracellular cyst(e)ine for the production of glutathione, a major cellular anti-oxidant. xCT is enriched in brain regions associated with neurogenesis. Previous studies have shown that the malfunction of this protein greatly attenuates cell proliferation in vitro and is associated with brain atrophy in vivo. Using mice that are homozygous for a function-blocking deletion in xCT (Sut mice), we examined in vivo the role of xCT in cell proliferation in neurogenic regions of the subventricular zone (SVZ) and denate gyrus (DG) in the adult brain. Our results indicate that a high level of cellular proliferation in the adult brain persists even in the absence of functional xCT. Furthermore, in both young adult and middle-aged mice (3 and 11 months old), rates of SVZ cell proliferation were comparable between Sut and wild-type controls, although there was trend towards reduced proliferation in Sut mice (12% and 9% reduction, respectively). To our surprise, rates of cell proliferation in the DG were elevated in both 3- and 11-month-old Sut mice relative to controls (22% and 28% increase, respectively). These results demonstrate that xCT expression plays a role in regulating cellular proliferation in the DG, but not the SVZ of adult mice. Furthermore, unlike previous in vitro studies, our in vivo observations clearly indicate that xCT is not essential for ongoing cellular proliferation.

• OSTI ID: 21033016
• Journal Information: Biochemical and Biophysical Research Communications, Vol. 364, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2007.10.036; PII: S0006-291X(07)02186-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ATROPHY
BRAIN
CELL PROLIFERATION
CYSTINE
GENE REGULATION
GLUTATHIONE
IN VITRO
IN VIVO
MICE
OXIDATION
OXIDIZERS