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Abnormal processing of Golgi elements and lysosomes in Tangier disease
1Institut für Arterioskleroseforschung, Westfälische Wilhelms-Universität, Münster, FRG.
Arteriosclerosis and Thrombosis : a Journal of Vascular Biology
|July 1, 1991
Summary
Tangier disease involves cellular defects affecting the Golgi apparatus and lysosomes, leading to abnormal lipid metabolism and intracellular traffic in mononuclear phagocytes and fibroblasts. This study reveals these abnormalities extend to Tangier fibroblasts, impacting cellular lipid processing.
Area of Science:
- Cell Biology
- Lipid Metabolism
- Genetic Disorders
Background:
- Tangier disease is characterized by defects in lipid metabolism and intracellular transport.
- Previous studies identified abnormalities in mononuclear phagocytes (MNPs) of Tangier patients.
- The specific cellular defects in Tangier fibroblasts remained less understood.
Purpose of the Study:
- To investigate the cellular and molecular defects in Tangier fibroblasts.
- To compare the abnormalities in Tangier fibroblasts with those in Tangier MNPs.
- To elucidate the role of the Golgi apparatus and lysosomes in Tangier disease pathogenesis.
Main Methods:
- Morphological analysis of MNPs and fibroblasts using electron microscopy.
- Immunoelectron microscopy to identify lysosomal compartments.
- Fluorescent ceramide analogue (C6-NBD-ceramide) labeling to study Golgi apparatus function.
- Tracer studies with tritiated choline to assess phospholipid synthesis and catabolism in fibroblasts.
Main Results:
- Tangier MNPs exhibited abnormal lysosomal vacuoles and Golgi apparatus dilation after lipid loading.
- Tangier fibroblasts showed increased incorporation of C6-NBD-ceramide and association with the cytoskeleton.
- Tangier fibroblasts displayed significantly higher sphingomyelin and phosphatidylcholine synthesis rates compared to controls.
Conclusions:
- The cellular defect in Tangier disease, described as a disorder of intracellular traffic, is also present in Tangier fibroblasts.
- Tangier disease is associated with morphological abnormalities in the Golgi apparatus and lysosomes, affecting cellular lipid metabolism.
- These findings highlight the widespread impact of the Tangier disease defect across different cell types and cellular compartments.