Effect of cutaneous permeability barrier disruption on HMG-CoA reductase, LDL receptor, and apolipoprotein E mRNA levels in the epidermis of hairless mice.
Disruption of the permeability barrier results in an increase in cholesterol synthesis in the epidermis. Inhibition of cholesterol synthesis impairs the repair and maintenance of barrier function. The increase in epidermal cholesterol synthesis after barrier disruption is due to an increase in the activity of epidermal HMG-CoA (3-hydroxy-3-methylglutaryl CoA) reductase. To determine the mechanism for this increase in enzyme activity, in the present study we have shown by Western blot analysis that there is a 1.5-fold increase in the mass of HMG-CoA reductase after acute disruption of the barrier with acetone. In a chronic model of barrier disruption, essential fatty acid deficiency, there is a 3-fold increase in the mass of HMG-CoA reductase. Northern blot analysis demonstrated that after acute barrier disruption with acetone or tape-stripping, epidermal HMG-CoA reductase mRNA levels are increased. In essential fatty acid deficiency, epidermal HMG-CoA reductase mRNA levels are increased 3-fold. Thus, both acute and chronic barrier disruption result in increases in epidermal HMG-CoA reductase mRNA levels which could account for the increase in HMG-CoA reductase mass and activity. Additionally, both acute and chronic barrier disruption increase the number of low density lipoprotein (LDL) receptors and LDL receptor mRNA levels in the epidermis. Moreover, epidermal apolipoprotein E mRNA levels are increased by both acute and chronic perturbations in the barrier. Increases in these proteins in response to barrier disruption may allow for increased lipid synthesis and transport between cells and facilitate barrier repair.
Jackson
S M
SM
Dermatology Service, Department of Veterans Affairs Medical Center, San Francisco, CA 94121.
Wood
L C
LC
Lauer
S
S
Taylor
J M
JM
Cooper
A D
AD
Elias
P M
PM
Feingold
K R
KR
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D015153:Blotting, Western; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D007700:Kinetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010539:Permeability / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism*; D011973:Receptors, LDL / Q000235:genetics*
D001057:Apolipoproteins E; D012333:RNA, Messenger; D011973:Receptors, LDL; D000096:Acetone; D006903:Hydroxymethylglutaryl CoA Reductases