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Effect of Oxysterol Treatment on Cholesterol Biosynthesis and Reactive Astrocyte Proliferation in Injured Rat Brain Cortex
Author(s) -
Bochelen D.,
Mersel M.,
Behr P.,
Lutz P.,
Kupferberg A.
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65052194.x
Subject(s) - oxysterol , astrogliosis , cholesterol , astrocyte , endogeny , medicine , cell growth , in vivo , liver x receptor , endocrinology , chemistry , biology , biochemistry , central nervous system , transcription factor , microbiology and biotechnology , nuclear receptor , gene
We have reported previously that oxysterols inhibit astrogliosis and intracranial glioblastoma growth. To elucidate the mechanism of action of these molecules in vivo, we have investigated their effect on the cholesterol biosynthesis in the injured brain. In a bilateral lesion model, injection of liposomes containing 7β‐hydroxycholesterol decreased [ 3 H]acetate incorporation into neutral lipids and cholesterol by 30% and 40%, respectively. Structural analogues were tested using a unilateral lesion model. The injury did not significantly affect cholesterogenesis; injection of 7β‐hydroxycholesterol or 7β‐hydroxycholesteryl‐3‐oleate reduced acetate incorporation into cholesterol by 47% and 43%, respectively. Both 7‐ketocholesteryl‐3‐oleate and 7α‐hydroxycholesteryl‐3‐oleate inhibited cholesterogenesis by 32%. As cholesterol and by‐products of the cholesterol pathway play a key role in cell division, we have assessed the effect of oxysterols on reactive astrocyte proliferation. The incorporation of bromodeoxyuridine showed that up to 46% of astrocytes were proliferating 24 h after the injury. Injection of 12 nmol of 7β‐hydroxycholesterol or 7β‐hydroxycholesteryl‐3‐oleate reduced the labelling index to 26%, whereas the labelling index in the 7‐ketocholesteryl‐3‐oleate‐treated cortex was 37%. These findings demonstrate that oxysterols are potent inhibitors of the endogenous cholesterol biosynthesis in brain and show a correlation between cholesterogenesis and reactive astrocyte proliferation.