Disease relevance of 7alpha-Hydroxycholesterol

• METHODS: Cholestyramine (12 g/day) was administered for 3 days to patients with compensated liver cirrhosis (n = 7), patients with chronic hepatitis (n = 10), and control subjects (n = 9), and serum total 7alpha-hydroxycholesterol level was measured by gas-liquid chromatography-mass spectrometry [1].
• In patients with primary biliary cirrhosis, serum 7alpha-hydroxycholesterol was slightly higher than in controls [2].

High impact information on 7alpha-Hydroxycholesterol

• Noteworthy, 7alpha-hydroxycholesterol induced only a slight inhibition of cell growth [3].
• Serum levels of 7alpha-hydroxycholesterol were unaffected, suggesting a normal rate of bile acid formation in the pathway involving cholesterol 7alpha-hydroxylase [4].
• The conversion of cholesterol to 7alpha-hydroxycholesterol catalyzed by cytochrome P450 7A1 (CYP7A1) initiates the major pathway for cholesterol elimination in mammals [5].
• In addition, P450 46A1 was able to carry out side chain hydroxylations of two endogenous C27-steroids with and without a double bond between C5-C6 (7alpha-hydroxycholesterol and cholestanol, respectively) and introduce a hydroxyl group on the steroid nucleus of the C21-steroid hormones with the C4-C5 double bond (progesterone and testosterone) [6].
• Cells expressing cholesterol-7alpha-hydroxylase displayed greater activities of luciferase reporters containing the SREBP-dependent promoter elements derived from HMG-CoA reductase and farnesyl diphosphate synthase, in spite of accumulating significantly more free and esterified cholesterol and 7alpha-hydroxycholesterol [7].

Chemical compound and disease context of 7alpha-Hydroxycholesterol

• Serum levels of 7alpha-hydroxycholesterol and 27-hydroxycholesterol have been measured in 25 patients (either normocholesterolemic or hypercholesterolemic) with primary biliary cirrhosis and in control subjects [2].

Biological context of 7alpha-Hydroxycholesterol

• All compounds, except 7alpha-hydroxycholesterol, induced apoptosis characterized by the occurrence of cells with fragmented and/or condensed nuclei, loss of mitochondrial potential, caspase-3 activation, PARP degradation, and internucleosomal DNA fragmentation [8].
• As surrogate markers of liver function, 7alpha-hydroxycholesterol and prealbumin concentrations and the plasma prothrombin time were determined [9].
• Serum 7alpha-hydroxycholesterol levels during liver regeneration after hepatectomy in humans [10].

Anatomical context of 7alpha-Hydroxycholesterol

• Incubations of rat liver subcellular preparations (containing microsomes) with [7alpha-3H]cholesterol or [7alpha,7beta-3H]cholesterol release the labeled hydrogen in the 7alpha position as 3H2O which, after counting, allows for the determination of the fraction of exogenous cholesterol converted to 7alpha-hydroxycholesterol [11].
• This study examined the effects of various drugs and sterols on the rate of 7alpha-hydroxycholesterol synthesis in isolated rat liver microsomes [12].
• The metabolism of 7alpha-hydroxycholesterol and 7alpha-hydroxy-beta-sitosterol (24alpha-ethyl-5-cholestene-3beta,7alpha-diol) has been compared in rat liver subcellular fractions [13].
• The distribution of 14C in the tissues and body fluids of control and vitamin-deficient guinea pigs injected with labelled 7alpha-hydroxycholesterol was likewise the same [14].

Associations of 7alpha-Hydroxycholesterol with other chemical compounds

• The results suggest that microsomal enzyme activity in the conversion of 7alpha-hydroxycholesterol to 7-ketocholesterol varies considerably, even within the subfamily Cricetinae and the family Muridae [15].
• However, in the rat-like hamster and the hispid cotton rat, 7alpha-hydroxycholesterol was converted mostly to 7alpha-hydroxy-4-cholesten-3-one, as also observed in the rat (Rattus norvegicus) [15].
• The assay was based on the measurement of mevalonolactone (MVL) and 7alpha-hydroxycholesterol (7alpha-OHC) produced by the incubation of HMG-CoA with hepatic microsomes in the presence of NADPH and glucose-6-phosphate dehydrogenase [16].

Gene context of 7alpha-Hydroxycholesterol

• Conversely, accumulation of the oxysterol 7alpha-hydroxycholesterol in the microsomes after CYP7A1 overexpression was correlated with a decrease in HMGR activity [17].
• However, in statin-treated patients, the circulating levels of 7beta- and 7alpha-hydroxycholesterol tend towards normal values [18].

Analytical, diagnostic and therapeutic context of 7alpha-Hydroxycholesterol

• Microsomal fractions were prepared from their livers, and the activities of the enzymes that participate in the dehydrogenation of 7alpha-hydroxycholesterol were determined by measuring the products using high-performance liquid chromatography [15].
• High circulating levels of 7beta- and 7alpha-hydroxycholesterol and presence of apoptotic and oxidative markers in arterial lesions of normocholesterolemic atherosclerotic patients undergoing endarterectomy [18].

References