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Titolo:
Mannose supplementation corrects GDP-mannose deficiency in cultured fibroblasts from some patients with Congenital Disorders of Glycosylation (CDG)
Autore:
Rush, JS; Panneerselvam, K; Waechter, CJ; Freeze, HH;
Indirizzi:
Burnham Inst, La Jolla, CA 92037 USA Burnham Inst La Jolla CA USA 92037Burnham Inst, La Jolla, CA 92037 USA Univ Kentucky, Albert B Chandler Med Ctr, Coll Med, Dept Biochem, Lexington, KY 40536 USA Univ Kentucky Lexington KY USA 40536 ept Biochem, Lexington, KY 40536 USA
Titolo Testata:
GLYCOBIOLOGY
fascicolo: 8, volume: 10, anno: 2000,
pagine: 829 - 835
SICI:
0959-6658(200008)10:8<829:MSCGDI>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHOMANNOSE ISOMERASE DEFICIENCY; LIPID-LINKED OLIGOSACCHARIDE; GLYCOPROTEIN SYNDROME TYPE-1; HAMSTER OVARY CELLS; SYNDROME TYPE-I; ENDOPLASMIC-RETICULUM; PROTEIN GLYCOSYLATION; GLUCOSE STARVATION; ABNORMAL SYNTHESIS; SERUM TRANSFERRIN;
Keywords:
GDP-mannose; mannose; Congenital Disorders of Glycosylation (CDG); fibroblast; phosphomannose isomerase;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Freeze, HH Burnham Inst, 10901 N Torrey Pines Rd, La Jolla, CA 92037 USA Burnham Inst 10901 N Torrey Pines Rd La Jolla CA USA 92037 USA
Citazione:
J.S. Rush et al., "Mannose supplementation corrects GDP-mannose deficiency in cultured fibroblasts from some patients with Congenital Disorders of Glycosylation (CDG)", GLYCOBIOLOG, 10(8), 2000, pp. 829-835

Abstract

Congenital Disorders of Glycosylation (CDC) are human deficiencies in glycoprotein biosynthesis. Previous studies showed that 1 mM mannose corrects defective protein N-glycosylation in cultured fibroblasts from some CDG patients. We hypothesized that these CDG cells have limited GDP-mannose (GDP-Man) and that exogenous mannose increases the GDP-Man levels. Using a well established method to measure GDP-Man, we found that normal fibroblasts had an average of 23.5 pmol GDP-Man/10(6) cells, whereas phosphomannomutase (PMM)-deficient fibroblasts had only 2.3-2.7 pmol/10(6) cells. Adding 1 mM mannose to the culture medium increased the GDP-Man level in PMM-deficient cells to approximately 15.5 pmol/10(6) cells, but had no significant effect on GDP-Man levels in normal fibroblasts. Similarly, mannose supplementation increased GDP-Man from 4.6 pmol/10(6) cells to 24.6 pmol/10(6) cells in phosphomannose isomerase (PMI)-deficient fibroblasts, Based on the specific activity of the GDP[H-3]Man pool present in [2-H-3]mannose labeled cells, mannose supplementation also partially corrected the impaired synthesis of mannosylphosphoryldolichol (Man-P-Dol) and Glc(0.3)Man(9)GlcNAc(2)-P-P-Dol. These results confirm directly that deficiencies in PMM and PMI result in lowered cellular GDP-Man levels that are corrected by the addition of mannose, In contrast to these results, GDP-Man levels in fibroblasts from a CDG-Ie patient, who is deficient in Man-P-Dol synthase, were normal and unaffected by mannose supplementation even though mannose addition was found to correctabnormal lipid intermediate synthesis in another study (Kim et al, [2000] J, Clin, Invest., 105, 191-198). The mechanism by which mannose supplementation corrects abnormal protein N-glycosylation in Man-P-Dol synthase deficient cells is unknown, but this observation suggests that the regulation of Man-P-Dol synthesis and utilization may be more complex than is currently understood.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 05/12/20 alle ore 10:41:28