Abstract
It has been postulated that hyperlipidemia in the nephrotic syndrome is due to overproduction of lipoproteins and that low colloid osmotic pressure (due to hypoalbuminemia) triggers this. Secretion of very low density lipoproteins (VLDL) by cultured rat hepatocytes has been shown to be inhibited by albumin, globulins, and dextrans, but the effect did not correlate with osmolarity. In the present studies we tested the hypothesis that viscosity rather than osmolarity might be the parameter determining the effectiveness of macromolecules in inhibiting VLDL synthesis and secretion by cultured rat hepatocytes. Synthesis and secretion of VLDL was measured in terms of incorporation of [3H] glycerol into medium triglycerides and also from changes in the mass of secreted VLDL triglycerides and apoproteins. The viscosity of the culture medium was increased by addition of dextran-500, gelatin or methylcellulose MX 880. Synthesis and secretion of VLDL was inhibited in direct proportion to increasing viscosity. At a viscosity of 2, which is about that of normal plasma, VLDL secretion was reduced by 20%. An inhibition of 60-70% in secretion and 30-40% in synthesis of VLDL lipid and protein components was observed at a relative viscosity of approximately 3.7. This viscosity was obtained by addition of any of the following: 3% dextran, 3% gelatin, 0.2% methylcellulose, or a combination of 0.1% methylcellulose plus 2% gelatin. Thus, similar viscosities resulted in similar degrees of inhibition despite differences of up to 16-fold in mass concentration and up to 20-fold in osmolarity.
Highlights
This workwas supported by National Institutes of Health research Grants HL-14197 and HL-15427, Public Health Service/Department of Health and HumanServices
Changes in plasma viscosity are likely to occur in hypoproteinemic states, especially in the nephrotic syndrome where albumin, fibrinogen, and otherhigh molecular weight proteins are lost to theurine (13) as the hyperlipidemia develops (14).The possibility that plasma viscosity is a regulator of the level of plasma protein is tested here
The final eluate containing fibronectin was extensively dialyzed against 1 M urea in Tris buffer and stored at 4 “C. Culture dishes were coated with fibronectin by incubation with 20-25 po1f the fibronectin preparation in 1.5ml of DME medium for at least 30 min at 37 ”C
Summary
Vol 257, No 5, Issue of March 10, pp. 2188-2192, 1982 Prrnled in L’.S.A. Viscosity of Culture Medium as a Regulator of Synthesis and Secretion of Very Low Density Lipoproteinsby Cultured Hepatocytes*. Levels of apoproteins (apo-B and C-1113) were measured by radioimmunoassay (19,20).Low density lipoprotein, used as a standard and for iodination, were isolated from plasma of adult male rats by zonal ultracentrifugation (21, 22). The density of the solutions was measured by weighing known volumes ( z ) and the relative viscosity was calculated according to theequation: vr = = t,p, tup, The effect of medium viscosity on the secretion of TG into the incubation mediumis shown in Fig.. Both incorporation of ['Hlglycerol into medium T G and the accumulationof TG mass in the medium were markedly decreased upon increasing the relative viscosity of the culture medium.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
