title: The 1,25D3 -MARRS receptor/PDIA3/ERp57 and lifespan.
abstract: Using MRI on mice bearing a targeted knockout (KO) of the 1,25D3 -MARRS receptor/PDIA3/ERp57 we found that they had decreased body fat relative to their littermate (LM) controls, a condition associated with increased lifespan. Others have found that lower body fat is correlated with decreased lipid droplets in intestinal cells that may be mediated by a factor secreted by germ cells (possibly estradiol). In a reducing environment estradiol competed for binding to the 1,25D3-MARRS receptor/PDIA3/ERp57. A consequence of this was that estradiol stimulated calcium uptake in enterocytes isolated from LM mice. In time course studies, lipid droplets increased in response to 1 nM estradiol from 1-5 D of culture, relative to corresponding controls, while at 6 and 7 D this steroid decreased lipid droplets. Enterocytes from LM or KOs incubated with estradiol for 1-4 D showed the hormone increased lipid droplets. Using the 4 D culture period, 1 and 10 nM estradiol significantly increased the number of lipid droplets in cells from LM mice by 40-60%, compared to equivalent conditions in KO mice. In assessing signal transduction pathways, the hormone increased phospho-Akt levels, but no differences were observed in phospho-mTORC1, or phospho-S6K (although cells from chicks did exhibit a hormone-mediated difference). Finally, the remaining mice (which had stopped reproducing) were allowed to die naturally and lifespan recorded. LM mice lived 687 ± 77 D (without an outlying value) while KO mice lived 740 D ± 80 D. These data suggest the 25D3 -MARRS receptor/PDIA3/ERp57 may contribute to the length of lifespan in mammals.
authors.affiliation: Department of Nutrition, Dietetics and Food Sciences, Utah State University, Logan, UT.
authors.forename: Ilka
authors.initials: I
authors.lastname: Nemere
authors.forename: Natalio
authors.initials: N
authors.lastname: Garbi
authors.forename: Quinton
authors.initials: Q
authors.lastname: Winger
mesh_terms: D050154:Adiposity; D000818:Animals; D015153:Blotting, Western; D002117:Calcitriol / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002469:Cell Separation; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D007422:Intestines / Q000166:cytology; D008136:Longevity; D008279:Magnetic Resonance Imaging; D008297:Male; D018345:Mice, Knockout; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding / Q000187:drug effects; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D019893:Ribosomal Protein S6 Kinases / Q000378:metabolism; D013194:Staining and Labeling; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D004958:Estradiol; D019893:Ribosomal Protein S6 Kinases; D058570:TOR Serine-Threonine Kinases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases; D002117:Calcitriol; D002118:Calcium
keywords: ESTRADIOL; LONGEVITY; MEMBRANE RECEPTORS; NON GENOMIC EFFECTS; VITAMIN D