Intestinal aminooligopeptidase in diabetic BioBreed rat: altered posttranslational processing and trafficking.
The structure of aminooligopeptidase (AOP), an intestinal brush-border digestive hydrolase, is abnormal in human diabetes and in the congenitally diabetic BioBreed Wistar (BB(d)) rat. Its assembly in the BB(d) rat was examined. After normal initial synthesis and assembly of immature AOP precursor (AOP(i)) 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 (AOP(m)) 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 AOP(m) of the diabetic rat. Intrajejunal pulse-chase experiments revealed that the conversion of AOP(i) to AOP(m) 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.
Najjar
S M
SM
Department of Medicine, Stanford University School of Medicine, Stanford, California 94305, USA. snajjar@mco.edu
Broyart
J P
JP
Hampp
L T
LT
Gray
G M
GM
D000818:Animals; D018826:CD13 Antigens / Q000235:genetics / Q000378:metabolism*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D020895:Enterocytes / Q000201:enzymology; D005260:Female; D006031:Glycosylation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007583:Jejunum / Q000166:cytology / Q000201:enzymology*; D007700:Kinetics; D007930:Leucine / Q000493:pharmacokinetics; D008297:Male; D008358:Mannose / Q000378:metabolism; D008715:Methionine / Q000493:pharmacokinetics; D008871:Microvilli / Q000201:enzymology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D013462:Sulfur Radioisotopes; D014316:Tritium
D013462:Sulfur Radioisotopes; D014316:Tritium; D008715:Methionine; D018826:CD13 Antigens; D007930:Leucine; D008358:Mannose