Effect of the knockdown of amyloid precursor protein on intracellular calcium increases in a neuronal cell line derived from the cerebral cortex of a trisomy 16 mouse.
Murine trisomy 16 (Ts16) is a useful model to study the deleterious effect of aneuploidy in neural pathophysiology. The CTb cell line derived from the cerebral cortex of a Ts16 mouse overexpresses the amyloid precursor protein (APP) and exhibits altered intracellular Ca(2+) homeostasis. In the present work, we induced knockdown of APP by transfecting specific mRNA antisense sequences into CTb cells. Forty-eight hours after transfection, the APP expression was knocked down by 40%, reaching levels comparable to those of the cortical line CNh, derived from a normal animal. Calcium measurements showed that the APP knockdown decreased intracellular Ca(2+) basal levels and accelerated the kinetics of the decay of Ca(2+) responses induced by glutamatergic agonists, nicotine, depolarization or ionomycin, to levels similar to those previously reported for CNh cells. The present results suggest that APP overexpression plays an important role on the altered intracellular Ca(2+) homeostasis in the trisomic cells.
Rojas
Guillermo
G
Program of Molecular & Clinical Pharmacology, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.
Cárdenas
Ana María
AM
Fernández-Olivares
Paola
P
Shimahara
Takeshi
T
Segura-Aguilar
Juan
J
Caviedes
Raúl
R
Caviedes
Pablo
P
D016564:Amyloid beta-Protein Precursor / Q000235:genetics*; D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000502:physiology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology; D016372:RNA, Antisense / Q000235:genetics; D017470:Receptors, Glutamate / Q000187:drug effects; D014314:Trisomy / Q000235:genetics*
D016564:Amyloid beta-Protein Precursor; D018690:Excitatory Amino Acid Agonists; D007476:Ionophores; D018722:Nicotinic Agonists; D016372:RNA, Antisense; D017470:Receptors, Glutamate; D015759:Ionomycin; D009538:Nicotine; D002118:Calcium