Increased oxysterols associated with iron accumulation in the brains and visceral organs of acaeruloplasminaemia patients

Abstract

Acaeruloplasminaemia is characterized by excessive neurovisceral iron accumulation due to mutation of the caeruloplasmin gene. Excess iron functions as a potent catalyst of biological oxidation, and increased iron concentration is associated with the products of lipid peroxidation in the serum and cerebrospinal fluid. We investigated whether the amount of iron accumulated paralleled lipid peroxidation levels in acaeruloplasminaemia tissues, examining brains and visceral organs of two affected patients at autopsy for iron and copper content, and oxysterols, including 7-hydroxycholesterol and 7-ketocholesterol, which are directly produced from cholesterol by active oxygen species. The amount of iron accumulated in various tissues was correlated with the levels of the oxysterols. These findings suggest that lipid peroxidation produced by the intracellular accumulation of iron is involved in the pathogenesis of acaeruloplasminaemia.

Analysis of oxysterols and vitamin D metabolites in mouse brain and cell line samples by ultra-high-performance liquid chromatography-atmospheric pressure photoionization–mass spectrometry

“…7␣-OH-Chl/7␤-OH-Chl (103-136 ng g −1 ) and 7-OXO (∼60 ng g −1 ) were also detected in the mouse brain samples. These compounds have previously been identified in human brain samples as well [34,37]. One noteworthy analyte, namely 25-OH-D 3 , was detected in all of the brain samples at low concentrations (∼4 ng g −1 ) using SRM transitions of m/z 401 → m/z 105 and m/z 133.…”

Glucose and Oxygen Hypometabolism in Aceruloplasminemia Brains.

“…1 N HC1. Sample solutions were analyzed directly in an atomic absorption spectrophotometer (Hitachi Z-6100, Tokyo) as described previously (15). Data was calculated on a dry weight basis because tissue density was not uniform in all the brain areas.…”

Cerebellar ataxia associated with heteroallelic ceruloplasmin gene mutation

“…21 Results. Brains and visceral organs were obtained at autopsy within 9 hours of death from Patients 1 and 3, and an aceruloplasminemia patient, as well as from four control subjects, mean age 68 years (two men and two women, 65 to 71 years old).…”