PMID- 7512790
OWN - NLM
STAT- MEDLINE
DCOM- 19940516
LR  - 20181113
IS  - 0002-9440 (Print)
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Linking)
VI  - 144
IP  - 4
DP  - 1994 Apr
TI  - Amyloid beta precursor protein and ubiquitin epitopes in human and experimental 
      dystrophic axons. Ultrastructural localization.
PG  - 702-10
AB  - Dystrophic axons (DA) represent a major pathological feature of several 
      neurodegenerative disorders, including infantile neuroaxonal dystrophy (INAD) and 
      Alzheimer disease. We have previously presented evidence that amyloid beta 
      precursor protein (BPP) and ubiquitin (Ub) are present in DA of different origin. 
      We have now characterized the immunoreactivity of DA experimentally induced in 
      rat by the administration of parabromophenylacetylurea (BPAU) and examined the 
      subcellular localization of Ub and BPP in BPAU-induced DA and in DA present in 
      subjects affected by INAD. BPAU-induced DA strongly immunoreacted with antisera 
      to Ub and to COOH- and NH2-terminal regions of BPP. Immunoblots of DA-enriched 
      brain regions were consistent with an increase in the amount of Ub and BPP in DA. 
      Moreover, BPAU-induced DA immunoreacted with antibodies to PGP 9.5, a 
      neuronal-specific Ub COOH-terminal hydrolase, and to the inducible heat shock 
      protein 70. Antigenic characterization also indicated that the tubulovesicular 
      membranes within DA derived largely from the smooth endoplasmic reticulum rather 
      than from the Golgi system or the synaptic vesicles. Subcellular 
      immunolocalization of Ub and BPP in both INAD- and BPAU-induced DA revealed that 
      Ub and BPP colocalize in granulovesicular material in both conditions. In INAD DA 
      intense Ub immunoreactivity was also detected in nonmembranous electron dense 
      structures that were present only in these DA, probably because of the chronic 
      course of INAD. Although BPP immunostaining may be related to accumulation of 
      BPP-containing membranes in DA, Ub immunostaining is likely to result from 
      activation of the Ub system by the neuron in the attempt to remove excessive and 
      possibly abnormal proteins. A similar pathogenesis can be postulated for DA of 
      Alzheimer disease.
FAU - Bacci, B
AU  - Bacci B
AD  - Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 
      44106.
FAU - Cochran, E
AU  - Cochran E
FAU - Nunzi, M G
AU  - Nunzi MG
FAU - Izeki, E
AU  - Izeki E
FAU - Mizutani, T
AU  - Mizutani T
FAU - Patton, A
AU  - Patton A
FAU - Hite, S
AU  - Hite S
FAU - Sayre, L M
AU  - Sayre LM
FAU - Autilio-Gambetti, L
AU  - Autilio-Gambetti L
FAU - Gambetti, P
AU  - Gambetti P
LA  - eng
GR  - NIA ADRC AG-08042-02/AG/NIA NIH HHS/United States
GR  - NIA R01 AGN-508155-02/AG/NIA NIH HHS/United States
GR  - NINCDS NS 14509-13/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (Epitopes)
RN  - 0 (Ubiquitins)
RN  - 8W8T17847W (Urea)
SB  - IM
MH  - Amyloid beta-Protein Precursor/*metabolism
MH  - Animals
MH  - Axons/*metabolism/ultrastructure
MH  - Central Nervous System Diseases/chemically induced/*metabolism/pathology
MH  - Disease Models, Animal
MH  - Epitopes/*metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Immunoenzyme Techniques
MH  - Male
MH  - Microscopy, Immunoelectron
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Ubiquitins/*metabolism
MH  - Urea/analogs & derivatives
PMC - PMC1887249
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
PMCR- 1994/10/01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
PHST- 1994/10/01 00:00 [pmc-release]
PST - ppublish
SO  - Am J Pathol. 1994 Apr;144(4):702-10.