Inhibition of sterol and DNA syntheses in phytohemagglutinin-stimulated human lymphocytes by 7.ALPHA.-hydroxycholesterol.

Abstract

Human Lymphocytes by 7a-Hydroxycholesterol. Tohoku J. exp. Med., 1985, 145(2), 105-113 Sterol and DNA syntheses were induced in human peripheral blood lymphocytes stimulated with phytohemagglutinin (PHA). DNA synthesis in the PHAstimulated lymphocytes was suppressed by 7a-hydroxycholesterol (7a-HC). The maximum suppression of DNA synthesis was observed when 7a-HC was added in the culture within 6 hr of PHA stimulation to the lymphocytes. However, as the concentration of fetal bovine serum (FBS) in the culture medium was increased, the inhibitory effect of 7a-HC on the syntheses of sterol and DNA were decreased. Furthermore, low and high density lipoproteins completely reversed the inhibition of DNA synthesis by 7a-HC. These results suggest that cholesterol is an essential requirement of lymphocyte blastogenesis regardless of whether the source of the sterol is exogenous or endogenous. lymphocyte blastogenesis ; 7a-hydroxycholesterol ; sterol synthesis ; DNA synthesis ; lipoproteins The activation of sequential metabolic pathways in lymphocytes is stimulated by phytohemagglutinin (PHA), concanavalin A, and lipopolysaccarides (Ling and Kay 1975). Sterol and DNA synthesis during blastogenesis of lymphocytes are suppressed by the addition of 25-hydroxycholesterol and 20a-hydroxycholesterol (Chen et al. 1975 ;Pratt et al. 1977). Oxygenated cholesterol derivatives such as 7a-hydroxycholesterol (7a-HC), 7f-hydroxycholesterol, 7-ketocholesterol, 20a-hydroxycholesterol, and 25-hydroxycholesterol regulate sterol synthesis in normal and malignant mammalian cell lines at the site of the reaction catalyzed by 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG

Cytotoxic effects of oxysterols associated with human diseases: Induction of cell death (apoptosis and/or oncosis), oxidative and inflammatory activities, and phospholipidosis

“…These suppressor activities are caused by inhibition of de novo biosynthesis of sterols. Indeed, cholesterol is required for the proliferation and cytotoxicity of lymphocytes (Cuthbert and Lipsky, 1980;Heiniger and Marshall, 1982;Hemmi et al, 1985). It was also shown that the lytic function of NK cells is sensitive to physical alterations of their plasma membrane induced by oxysterols (Kucuk et al, 1992) and that the inhibition of the cytolytic activity of lymphocytes by oxysterols is due to the replacement of membrane cholesterol by oxysterols, thus altering the physical functions of the plasma membrane (Kucuk et al, 1994).…”

Critical evaluation of the safety of Cimicifuga racemosa in menopause symptom relief

“…Hemmi and colleagues 58 tested the effect of Cimicifuga (formulation unspecified) on the uptake of labeled thymidine into phytohemagglutinin-stimulated lymphocytes and mouse lymphosarcoma L-5178 cells and demonstrated that Cimicifuga selectively inhibits the uptake of uridine, adenosine, and thymidine without inhibiting mitosis or DNA synthesis.…”