Effect of centrophenoxine and BCE-001 treatment on lateral diffusion of proteins in the hepatocyte plasma membrane as revealed by fluorescence recovery after photobleaching in rat liver smears.
The average lateral diffusion coefficient of proteins (D) in the cell membrane of hepatocytes has been measured in liver smears by fluorescence recovery after photobleaching (FRAP), based on the so-called peroxide-induced autofluorescence (PIAF) deriving from the oxidation of riboflavin bound to membrane proteins. It has been previously shown that D displays a significant negative linear age correlation. The in vivo effects of two drugs were tested on this parameter. Young (2.7 months) and old (24-26 months) male rats received centrophenoxine (CPH) or a new drug (BCE-001) by either intraperitoneal (i.p.) injection or per os through a gastric tube for 26 to 42 days. D was measured on a double-blind basis in the hepatocyte plasma membrane of treated and control groups. The CPH and BCE-001 treatments did not affect the value of D in the young rats. However, the latter drug increased their growth rate. An increase of D in old animals was induced by treatment with either drug. When the drug effects in old rats were compared, BCE-001 proved to be more efficient than CPH, and at the same time was able to significantly retard the age-dependent loss of body weight characteristic of these animals at the age of approximately 2 years. Our results are in good accord with the predictions of the membrane hypothesis of aging as regards the role of properly placed OH. free radical scavengers in the improvement of membrane and overall cell function.
Zs-Nagy
I
I
First Laboratory of Clinical Physiology, Tokyo Metropolitan Institute of Gerontology, Japan.
Ohta
M
M
Kitani
K
K
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects*; D005453:Fluorescence; D005609:Free Radicals; D006016:Glycolates / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D002504:Meclofenoxate / Q000494:pharmacology* / Q000031:analogs & derivatives; D008565:Membrane Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D015262:Xenobiotics / Q000494:pharmacology*
D005609:Free Radicals; D006016:Glycolates; D008565:Membrane Proteins; D015262:Xenobiotics; C061781:BCE 001; D002504:Meclofenoxate