English
Albanian
Arabic
Armenian
Azerbaijani
Belarusian
Bengali
Bosnian
Catalan
Czech
Danish
Deutsch
Dutch
English
Estonian
Finnish
Français
Greek
Haitian Creole
Hebrew
Hindi
Hungarian
Icelandic
Indonesian
Irish
Italian
Japanese
Korean
Latvian
Lithuanian
Macedonian
Mongolian
Norwegian
Persian
Polish
Portuguese
Romanian
Russian
Serbian
Slovak
Slovenian
Spanish
Swahili
Swedish
Turkish
Ukrainian
Vietnamese
Български
中文(简体)
中文(繁體)
Biochemical Journal 1994-Jul

New pathogenetic hypothesis for Wolman disease: possible role of oxidized low-density lipoproteins in adrenal necrosis and calcification.

Only registered users can translate articles
Log In/Sign up
The link is saved to the clipboard
G Fitoussi
A Nègre-Salvayre
M T Pieraggi
R Salvayre

Keywords

Abstract

Wolman disease in an inherited metabolic disease, characterized by a severe deficiency of the acid lipase and a massive lysosomal storage of triacylglycerols and cholesteryl esters, associated with hepatosplenomegaly, adrenal calcification and nearly always fatal in the first year of life. Cultured human lymphoblastoid cells and human adrenal cells are able to promote the formation of mildly oxidized low-density lipoproteins (LDL), which in turn exhibit a non-negligible cytotoxic effect on these cells. In contrast, fibroblasts induce only very low levels of LDL oxidation. Comparative experiments have shown that the cytotoxic effect of oxidized LDL was higher to Wolman-disease cells than to controls. The oxidative ability of Wolman cells was similar to that of normal ones. The over-cytotoxicity of mildly oxidized LDL to Wolman cells resulted from the higher uptake of mildly oxidized LDL through the LDL-receptor pathway, which is only poorly down-regulated in Wolman cells subsequently to the block of the lysosomal degradation of LDL-cholesteryl esters. In cultured adrenal cells, oxidized LDL induced a sustained rise in intracellular [Ca2+] which is directly involved in the cellular damage and cell death induced by oxidized LDL [Nègre-Salvayre and Salvayre (1992) Biochim. Biophys. Acta 1123, 207-215]. This Ca2+ peak is followed by a dramatic deposition of calcium in damaged or/and dead cultured adrenal cells, quite similar to that observed in Wolman-disease adrenal cortex. The cell-induced LDL oxidation and the subsequent cytotoxic effect can be prevented, at least in part, by antioxidants such as alpha-tocopherol and nordihydroguaiaretic acid. These findings support the hypothesis that the Wolman-disease adrenal damage (necrosis and calcification) could result from the association of the following events: mild oxidation of LDL by adrenal cells, over-uptake of mildly oxidized LDL by Wolman cells (resulting from the block of the lysosomal degradation of cholesteryl esters in Wolman cells), and cytotoxicity related to the amount of mildly oxidized LDL internalized by cells. The reported data also suggest that LDL oxidation induced by adrenal cells and their subsequent cytotoxicity can be prevented (in part) by antioxidants, and the potential therapeutic use of antioxidants in Wolman disease is discussed.

Join our facebook page

The most complete medicinal herbs database backed by science

  • Works in 55 languages
  • Herbal cures backed by science
  • Herbs recognition by image
  • Interactive GPS map - tag herbs on location (coming soon)
  • Read scientific publications related to your search
  • Search medicinal herbs by their effects
  • Organize your interests and stay up do date with the news research, clinical trials and patents

Type a symptom or a disease and read about herbs that might help, type a herb and see diseases and symptoms it is used against.
*All information is based on published scientific research

Google Play badgeApp Store badge