Amyloid beta-protein1-42 increases cAMP and apolipoprotein E levels which are inhibited by beta1 and beta2-adrenergic receptor antagonists in mouse primary astrocytes.
Amyloid beta-protein (Abeta) increases apolipoprotein E (apoE) levels in astrocytes which could alter lipid trafficking. The mechanism for the Abeta-induced increase in apoE levels is not well understood. It is well established that stimulation of beta-adrenergic receptors (betaARs) increases cAMP levels. Elevation of cAMP levels increases apoE abundance. The current study determined if Abeta(1-42) stimulation of cAMP and apoE levels could be inhibited by betaAR antagonists in astrocytes. We demonstrate that Abeta(1-42) but not the reverse protein Abeta(42-1) or Abeta(1-40) stimulated cAMP formation and this stimulation was inhibited by selective betaAR antagonists in mouse primary cortical astrocytes. Abeta(1-42) significantly increased apoE levels which were significantly inhibited by the betaAR selective antagonists with the greatest inhibition observed with the beta(2) antagonist. Separate lines of evidence have suggested that agonist-induced stimulation of betaARs and increases in apoE abundance may serve a neuroprotective role in astrocytes. Our results indicate a potential interaction between betaARs and apoE which may contribute to reducing Abeta(1-42) neurotoxicity.
Igbavboa
U
U
Geriatric Research, Education and Clinical Center, VA Medical Center and Department of Pharmacology, University of Minnesota School of Medicine, One Veterans Drive, Minneapolis, MN 55417, USA.
Johnson-Anuna
L N
LN
Rossello
X
X
Butterick
T A
TA
Sun
G Y
GY
Wood
W G
WG
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001057:Apolipoproteins E / Q000378:metabolism*; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D015870:Gene Expression / Q000187:drug effects; D007124:Immunoenzyme Techniques / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000494:pharmacology*; D013997:Time Factors
D000319:Adrenergic beta-Antagonists; D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000242:Cyclic AMP