Author/Editor		Fon-Tacer, Klementina
Title		Tkivno-specifično uravnavanje biosinteze holesterola v modih, jetrih in možganih v različnih fizioloških/patofizioloških pogojih
Translated title		Tissue specific regulation of cholesterol biosynthesis in the testes, liver and brain in different physiological/pathophysiological conditions
Type		monografija
Place		Ljubljana
Publisher		Univerza v Ljubljani, Medicinska fakulteta
Publication year		2005
Volume		str. 150
Language		slo
Abstract		Contemporary lifestyle leads to different metabolic disorders as obesity and diabetes that already have epidemic characteristics and often lead to cardio-vascular discascs. There is an increasing evidence that the pathogenesis is a result of interactions betwccn immune system and lipid metabolism. Therefore, we wanted to ascertain the impact of inflammatory cytokine TNFalpha on cholesterol homeostasis in the mouse livcr, brain and tcstes. We identified that sterol intermediates represent 1% of total liver and brain sterols, and 5% of testis sterols, mostly on account of T-MAS. Cholesterol biosynthesis in all three tissues of normally fed mice uses the branch with delta24-intermediates and desmosterol as the immediate precursor of cholesterol. Only in liver there are comparable amounts of desmosterol and 7-dehydrocholesterol, so we propose that in liver dhcr24 and dhcr7 compete for substrate cholesta-5,7;24-trien-3beta-ol. Cholesterol biosynthesis is regulated through the negative fcedback loop with transcription factors SREBP-2. Mature SREBP-2 protein was detected in mice liver and testis and was unregulated in liver of prepubertal as well as adult animals after food deprivation. In contrast to liver, up-regulation of SREBP-2 has been detected only in mature animals, which coincides with higher concentration of FFMAS as a direct product of SREBP-2 regulated gene cyp51. In addition to 68 kDa SREBP-2, three other SREBP-2 immunoreactive bands that are not dctected in mouse liver nuclei were found in the testes of prepubertal and adult mice. The 55 kDa protein is likely SREBP2gc, the other two isoforms are novel and all seem to be insensitive to the level of cholesterol. Fasting does not have a significant impact on the liver sterol metabolome, whereas in brain a decreased amount of all sterol intermediates, except lanosterol, has been detected. Reduction was statistically significant for T-MAS and zymosterol. (Abstract truncated at 2000 characters).
Descriptors		TESTIS LIVER BRAIN CHOLESTEROL TUMOR NECROSIS FACTOR STARVATION TUMOR CELLS, CULTURED CARCINOMA, HEPATOCELLULAR TRIGLYCERIDES LIPOPROTEINS, HDL CHOLESTEROL CHROMATOGRAPHY, HIGH PRESSURE LIQUID POLYMERASE CHAIN REACTION MICE, INBRED CBA MICE, INBRED C57BL