Journal article
Abnormal myo-inositol and phospholipid metabolism in cultured fibroblasts from patients with ataxia telangiectasia
Biochimica et biophysica acta. Molecular and cell biology of lipids, Vol.1437(3), pp.287-300
1999
DOI: 10.1016/S1388-1981(99)00022-0
PMID: 10101263
Abstract
Ataxia telangiectasia (AT) is a complex autosomal recessive disorder that has been associated with a wide range of physiological defects including an increased sensitivity to ionizing radiation and abnormal checkpoints in the cell cycle. The mutated gene product, ATM, has a domain possessing homology to phosphatidylinositol-3-kinase and has been shown to possess protein kinase activity. In this study, we have investigated how AT affects
myo-inositol metabolism and phospholipid synthesis using cultured human fibroblasts. In six fibroblast lines from patients with AT,
myo-inositol accumulation over a 3-h period was decreased compared to normal fibroblasts. The uptake and incorporation of
myo-inositol into phosphoinositides over a 24-h period, as well as the free
myo-inositol content was also lower in some but not all of the AT fibroblast lines. A consistent finding was that the proportion of
32P in total labeled phospholipid that was incorporated into phosphatidylglycerol was greater in AT than normal fibroblasts, whereas the fraction of radioactivity in phosphatidic acid was decreased. Turnover studies revealed that AT cells exhibit a less active phospholipid metabolism as compared to normal cells. In summary, these studies demonstrate that two manifestations of the AT defect are alterations in
myo-inositol metabolism and phospholipid synthesis. These abnormalities could have an effect on cellular signaling pathways and membrane production, as well as on the sensitivity of the cells to ionizing radiation and proliferative responses.
Details
- Title: Subtitle
- Abnormal myo-inositol and phospholipid metabolism in cultured fibroblasts from patients with ataxia telangiectasia
- Creators
- Mark A Yorek - Department of Internal Medicine, Diabetes-Endocrinology Research Center and Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52246, USAJoyce A Dunlap - Department of Internal Medicine, Diabetes-Endocrinology Research Center and Veterans Affairs Medical Center, University of Iowa, Iowa City, IA 52246, USAArturo Manzo-Fontes - Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5934, USARoberto Bianchi - Department of Molecular Biochemistry and Pharmacology, Mario Negri Institute, Milan, ItalyGerard T Berry - Department of Pediatrics, University of Pennsylvania School of Medicine, Division of Biochemical Development and Molecular Diseases and The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USAJoseph Eichberg - Department of Biology and Biochemistry, University of Houston, Houston, TX 77204-5934, USA
- Resource Type
- Journal article
- Publication Details
- Biochimica et biophysica acta. Molecular and cell biology of lipids, Vol.1437(3), pp.287-300
- Publisher
- Elsevier B.V
- DOI
- 10.1016/S1388-1981(99)00022-0
- PMID
- 10101263
- ISSN
- 1388-1981
- eISSN
- 1879-2618
- Language
- English
- Date published
- 1999
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984094598402771
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