Increased levels of the Kunitz protease inhibitor-containing beta APP mRNAs in rat brain following neurotoxic damage.
Deposits of beta-amyloid are one of the main pathological characteristics of Alzheimer's disease. The beta-amyloid peptide (or beta/A4) constituent of these deposits is derived from the beta-amyloid precursor protein (beta APP), which is expressed in several isoforms. It has been suggested that an imbalance in the normal ratio between the Kunitz protease inhibitor (KPI)-containing beta APPs versus the non containing forms could result in altered processing of beta APP and progressive beta/A4 deposition. We have studied the expression of four beta APP isoforms in the rat brain after intracerebroventricular application of kainic acid. Increased levels of the KPI-containing beta APP and GFAP mRNAs were observed in tissues surrounding areas of neuronal damage. A parallel increase of beta APP and GFAP immunoreactivity was observed in reactive astrocytes in these areas. These results suggest that the normal ratio of beta APP isoforms may be profoundly altered as a result of neuronal damage and that non-neuronal cells may respond to neuronal injury by increased expression of the KPI-containing beta APP isoforms.
Department of Neurochemistry, CID, CSIC, Barcelona, Spain.
C
C
Solà
F J
FJ
García-Ladona
G
G
Mengod
A
A
Probst
P
P
Frey
J M
JM
Palacios
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007527:Isoenzymes / Q000096:biosynthesis* / Q000235:genetics; D007608:Kainic Acid / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015842:Serine Proteinase Inhibitors / Q000096:biosynthesis*
D016564:Amyloid beta-Protein Precursor; D005904:Glial Fibrillary Acidic Protein; D007527:Isoenzymes; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D007608:Kainic Acid