Reversible ischemia increases levels of Alzheimer amyloid protein precursor without increasing levels of mRNA in the rabbit spinal cord.
In a rabbit spinal cord ischemia model (RSCIM), the time courses of neuropathological damage of the spinal cord and neurological impairment of the motor functions are well established, demonstrating that the extent of neuropathological damage and the severity of neurological impairment are closely correlated. We used the RSCIM to elucidate the effects of reversible (15 min) and irreversible (60 min) ischemia on the endogenous levels of amyloid protein precursors (APPs) at both the mRNA and protein levels in the caudolumbar/sacral region of the spinal cord. We speculate that endogenous APPs are induced by ischemia as either trophic factors or stress-induced proteins in the RSCIM. A 15-min occlusion transiently increased the APP protein levels in neurons, which returned to the original levels by the end of 60 min occlusion. The increase in APP protein levels during 15-min ischemic insult does not appear to involve regulation at the mRNA level. The increased level of APPs, particularly of the soluble form, could support the possibility that APPs play a neuroprotective role in the RSCIM as stress-induced proteins. In contrast, failure to maintain the increased APP protein levels or to increase the mRNA, as seen in the 60-min ischemia samples, may be one of the causal factors that induce necrosis and neuronal cell death leading to irreversible neurological impairment.
Komori
N
N
Department of Neurosciences, University of California at San Diego, La Jolla 92093-0624, USA.
Kittel
A
A
Kang
D
D
Shackelford
D
D
Masliah
E
E
Zivin
J A
JA
Saitoh
T
T
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis*; D000818:Animals; D001483:Base Sequence; D004195:Disease Models, Animal; D006801:Humans; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D051379:Mice; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D011817:Rabbits; D051381:Rats; D015424:Reperfusion; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013116:Spinal Cord / Q000098:blood supply* / Q000378:metabolism*; D013997:Time Factors; D014158:Transcription, Genetic
D016564:Amyloid beta-Protein Precursor; D012333:RNA, Messenger