title: Plasma zinc's alter ego is a low-molecular-weight humoral factor.
abstract: Mild dietary zinc deprivation in humans and rodents has little effect on blood plasma zinc levels, and yet cellular consequences of zinc depletion can be detected in vascular and other tissues. We proposed that a zinc-regulated humoral factor might mediate the effects of zinc deprivation. Using a novel approach, primary rat vascular smooth muscle cells (VSMCs) were treated with plasma from zinc-deficient (<1 mg Zn/kg) or zinc-adequate (35 mg Zn/kg, pair-fed) adult male rats, and zinc levels were manipulated to distinguish direct and indirect effects of plasma zinc. Gene expression changes were analyzed by microarray and qPCR, and incubation of VSMCs with blood plasma from zinc-deficient rats strongly changed the expression of >2500 genes, compared to incubation of cells with zinc-adequate rat plasma. We demonstrated that this effect was caused by a low-molecular-weight (∼2-kDa) zinc-regulated humoral factor but that changes in gene expression were mostly reversed by adding zinc back to zinc-deficient plasma. Strongly regulated genes were overrepresented in pathways associated with immune function and development. We conclude that zinc deficiency induces the production of a low-molecular-weight humoral factor whose influence on VSMC gene expression is blocked by plasma zinc. This factor is therefore under dual control by zinc.
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Rd., Bucksburn, Aberdeen AB21 9SB, Scotland, UK.
authors.forename: Ou
authors.initials: O
authors.lastname: Ou
authors.forename: Keith
authors.initials: K
authors.lastname: Allen-Redpath
authors.forename: Dagmar
authors.initials: D
authors.lastname: Urgast
authors.forename: Margaret-Jane
authors.initials: MJ
authors.lastname: Gordon
authors.forename: Gill
authors.initials: G
authors.lastname: Campbell
authors.forename: Jörg
authors.initials: J
authors.lastname: Feldmann
authors.forename: Graeme F
authors.initials: GF
authors.lastname: Nixon
authors.forename: Claus-Dieter
authors.initials: CD
authors.lastname: Mayer
authors.forename: In-Sook
authors.initials: IS
authors.lastname: Kwun
authors.forename: John H
authors.initials: JH
authors.lastname: Beattie
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D004435:Eating / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D008297:Male; D008970:Molecular Weight; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D016133:Polymerase Chain Reaction; D051381:Rats; D015032:Zinc / Q000097:blood* / Q000172:deficiency / Q000494:pharmacology*
chemical_list: D015032:Zinc
keywords: atherosclerosis; microarray; smooth muscle; zinc deficiency