S100 beta increases levels of beta-amyloid precursor protein and its encoding mRNA in rat neuronal cultures.
S100beta has been implicated in the formation of dystrophic neurites, overexpressing beta-amyloid precursor protein (betaAPP), in the beta-amyloid plaques of Alzheimer's disease. We assessed the effects of S100beta on cell viability of, neurite outgrowth from, and betaAPP expression by neurons in primary cultures from fetal rat cortex. S100beta (1-10 ng/ml) enhanced neuronal viability (as assessed by increased mitrochondrial activity and decreased lactic acid dehydrogenase release) and promoted neurite outgrowth. Higher levels of S100beta (100 ng/ml, but not 1 microg/ml) produced qualitatively similar, but less marked, effects. S100beta also induced increased neuronal expression of the microtubule-associated protein MAP2, an effect that is consistent with trophic effects of S100beta on neurite outgrowth. S100beta (10 and 100 ng/ml) induced graded increases in neuronal expression of betaAPP and of betaAPP mRNA. These results support our previous suggestion that excessive expression of S100beta by activated, plaque-associated astrocytes in Alzheimer's disease contributes to the appearance of dystrophic neurites overexpressing betaAPP in diffuse amyloid deposits, and thus to the conversion of these deposits into the diagnostic neuritic beta-amyloid plaques.
Li
Y
Y
Department of Geriatrics, University of Arkansas Medical Sciences, Little Rock, USA.
Wang
J
J
Sheng
J G
JG
Liu
L
L
Barger
S W
SW
Jones
R A
RA
Van Eldik
L J
LJ
Mrak
R E
RE
Griffin
W S
WS
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D002478:Cells, Cultured; D002540:Cerebral Cortex; D005333:Fetus; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins
D016564:Amyloid beta-Protein Precursor; D002135:Calcium-Binding Proteins; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D064568:S100 Calcium Binding Protein beta Subunit; D009418:S100 Proteins