Abstract
Congenital disorder of glycosylation Ia (CDGIa) is an autosomal recessive disease that is caused by mutations in the gene PMM2 encoding phosphomannomutase, an enzyme that synthesizes mannose-1-phosphate, an important intermediate for the N-glycan biosynthesis. Here, we investigated the susceptibility of CDGIa fibroblasts to cell death induction. CDGIa fibroblasts were more sensitive than control fibroblasts to staurosporine-induced apoptosis. Supplementation with mannose, which corrects N-glycosylation in CDGIa fibroblasts, did not abrogate their higher sensitivity to staurosporine. These results show that the sensitivity of CDGIa fibroblasts to apoptosis is not directly related to their defective N-glycosylation.
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Abbreviations
- CDGIa:
-
congenital disorder of glycosylation Ia
- endo H:
-
endo-β-N-acetylglucosaminidase H
- ER:
-
endoplasmic reticulum
- LLO:
-
lipid-linked oligosaccharides
- PARP:
-
poly-(ADP-ribose)polymerase
- z-VAD-fmk:
-
N-benzyloxycarbonyl-Val-Ala-(DL)Asp-fluoromethylketone
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Acknowledgements
We thank T. Dupré and N. Seta (Hôpital Bichat, Paris) for providing controls and CDGIa fibroblasts. Thanks are also due to S. Moore and Y. Pilatte for helpful comments on the manuscript.
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This work was supported by institutional funding from the Institut National de la Santé et de la Recherche Médicale (INSERM) and an INSERM-AFM research network grant (4MR39F) “Réseau de Recherche sur les CDG.”
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Lavieu, G., Frénoy, JP., Codogno, P. et al. Defect of N-Glycosylation Is Not Directly Related to Congenital Disorder of Glycosylation Ia Fibroblast Sensitivity to Staurosporine-Induced Cell Death. Pediatr Res 58, 254–257 (2005). https://doi.org/10.1203/01.PDR.0000169962.02462.C0
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DOI: https://doi.org/10.1203/01.PDR.0000169962.02462.C0
