Chaperone-mediated regulation of hepatic protein secretion by caloric restriction.
Calorie restriction (CR) delays age-related physiological changes, reduces cancer incidence, and increases maximum life span in mammals. Here we show that CR decreased the expression of many hepatic molecular chaperones and concomitantly increased the rate and efficiency of serum protein secretion. Hepatocytes from calorie-restricted mice secreted twice as much albumin, 63% more alpha1-antitrypsin, and 250% more of the 31.5-kDa protein 2 h after their synthesis. A number of trivial explanations for these results, such as differential rates of protein synthesis and cell leakage during the assay, were eliminated. These novel results suggest that CR may promote the secretion of serum proteins, thereby promoting serum protein turnover. This may reduce the circulating level of damaging, glycoxidated serum proteins.
Dhahbi
J M
JM
Department of Biochemistry, University of California, Riverside, Riverside, California 92521, USA.
Cao
S X
SX
Tillman
J B
JB
Mote
P L
PL
Madore
M
M
Walford
R L
RL
Spindler
S R
SR
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism*; D015153:Blotting, Western; D002135:Calcium-Binding Proteins / Q000378:metabolism; D037282:Calreticulin; D002352:Carrier Proteins / Q000378:metabolism; D002469:Cell Separation; D004032:Diet; D004591:Electrophoresis, Polyacrylamide Gel; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D002149:Energy Intake / Q000502:physiology*; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000378:metabolism; D007535:Isomerases / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D019704:Protein Disulfide-Isomerases; D012333:RNA, Messenger / Q000378:metabolism; D012346:RNA, Transfer, Amino Acyl / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism; D012709:Serum Albumin / Q000235:genetics / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000235:genetics / Q000378:metabolism
D001798:Blood Proteins; D002135:Calcium-Binding Proteins; D037282:Calreticulin; D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006023:Glycoproteins; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D012333:RNA, Messenger; D012346:RNA, Transfer, Amino Acyl; D012261:Ribonucleoproteins; D012709:Serum Albumin; D000515:alpha 1-Antitrypsin; C062477:endoplasmic reticulum glycoprotein p72; C098410:glucose-regulated protein 170; C026464:tRNA(m)(Met), methionine-; D007535:Isomerases; C513195:Pdia3 protein, mouse; D019704:Protein Disulfide-Isomerases