TY - JOUR
T1 - Regulation of protein synthesis in lymphoblasts from vanishing white matter patients
AU - Van Kollenburg, Barbara
AU - Thomas, Adri A.M.
AU - Vermeulen, Gerre
AU - Bertrand, Gesina A.M.
AU - Van Berkel, Carola G.M.
AU - Pronk, Jan C.
AU - Proud, Christopher G.
AU - Van Der Knaap, Marjo S.
AU - Scheper, Gert C.
N1 - Funding Information: We would like to thank all patients and their families for cooperation. Financial support for this work was provided by “Princes Beatrix Fonds” (PBF) (grant MAR01-0201), “Stichting Spieren voor Spieren”, Dr. W.M. Phelps Stichting (grant 00026WO), the Wellcome Trust, and the Optimix Foundation for Scientific Research. We thank Dr. F. Wiegant (Utrecht University) for the HSP72-antibody. We also thank Dr. Maarten Terlou (Utrecht University) for the quantification of the Western blots and Dr. P.D. Bezemer (VU University, Amsterdam) for helping with the statistical analysis of the data.
PY - 2006/3
Y1 - 2006/3
N2 - Leukoencephalopathy with vanishing white matter (VWM) is an inherited childhood white matter disorder, caused by mutations in the genes encoding eukaryotic initiation factor 2B (eIF2B). The present study showed that, while the eIF2B activity was reduced in VWM lymphoblasts, the expression levels of the eIF2B subunits were similar to control lymphoblast lines. The mutations in eIF2B did not affect the interaction with eIF2. Strikingly, no apparent differences for the regulation of protein synthesis, measured by [ 35S]-methionine incorporation, were found between control and VWM lymphoblasts. Western blotting showed that, in some VWM cells, exposure to heat shock caused a decrease in the expression of specific eIF2B subunits. Most importantly, the increase in phosphorylation of eIF2α in response to heat shock was lower in VWM lymphoblasts than in control cells. These findings could form part of the explanation for the episodes of rapid and severe deterioration in VWM patients that are precipitated by febrile infections.
AB - Leukoencephalopathy with vanishing white matter (VWM) is an inherited childhood white matter disorder, caused by mutations in the genes encoding eukaryotic initiation factor 2B (eIF2B). The present study showed that, while the eIF2B activity was reduced in VWM lymphoblasts, the expression levels of the eIF2B subunits were similar to control lymphoblast lines. The mutations in eIF2B did not affect the interaction with eIF2. Strikingly, no apparent differences for the regulation of protein synthesis, measured by [ 35S]-methionine incorporation, were found between control and VWM lymphoblasts. Western blotting showed that, in some VWM cells, exposure to heat shock caused a decrease in the expression of specific eIF2B subunits. Most importantly, the increase in phosphorylation of eIF2α in response to heat shock was lower in VWM lymphoblasts than in control cells. These findings could form part of the explanation for the episodes of rapid and severe deterioration in VWM patients that are precipitated by febrile infections.
KW - Childhood
KW - Heat shock
KW - Leukoencephalopathy
KW - Translation
KW - White matter
KW - eIF2B
UR - http://www.scopus.com/inward/record.url?scp=33244482231&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.nbd.2005.08.009
DO - https://doi.org/10.1016/j.nbd.2005.08.009
M3 - Article
C2 - 16185887
SN - 0969-9961
VL - 21
SP - 496
EP - 504
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -