Vol. 280, Issue 1, G104-G112, January 2001
Intestinal aminooligopeptidase in diabetic BioBreed
rat: altered posttranslational processing and trafficking
Sonia M.
Najjar1,2,
Jean-Pierre
Broyart1,
Lydia
T.
Hampp1, and
Gary M.
Gray1,3
1 Department of Medicine and 3 Digestive Disease
Center, Stanford University School of Medicine, Stanford,
California 94305; and 2 Department of Pharmacology and
Therapeutics, Medical College of Ohio, Toledo, Ohio 43614
The structure of
aminooligopeptidase (AOP), an intestinal brush-border digestive
hydrolase, is abnormal in human diabetes and in the congenitally
diabetic BioBreed Wistar (BBd) rat. Its assembly in the
BBd rat was examined. After normal initial synthesis and
assembly of immature AOP precursor (AOPi) with high-mannose N-linked chains in the endoplasmic reticulum (ER), processing of
N-linked glycans in Golgi yielded a smaller than normal mature AOP
precursor (AOPm) with persistence of some high-mannose
N-linked chains. Deglycosylation analyses suggested that the mass
difference could be attributed to a lower mass of N-linked with
unaltered O-linked glycans in AOPm of the diabetic rat.
Intrajejunal pulse-chase experiments revealed that the conversion of
AOPi to AOPm occurred at 30 min of chase in
normal rats but at 60-90 min in diabetic rats, reflecting delay in
ER-to-Golgi transport or a slower processing of high-mannose chains.
Once maximal transport to Golgi was achieved, the residence time in
Golgi was shortened in diabetes. This altered processing of the
precursor accounted for the altered structure of AOP in diabetes.
aminopeptidase N; kinetics; N-linked carbohydrates
