Huperzine A enhances the level of secretory amyloid precursor protein and protein kinase C-alpha in intracerebroventricular beta-amyloid-(1-40) infused rats and human embryonic kidney 293 Swedish mutant cells.
We examined whether huperzine A (HupA), a promising therapeutic agent for Alzheimer's disease, could alter the processing of amyloid precursor protein (APP) in rats with beta-amyloid protein-(1-40) (Abeta(1-40)) infusion into the cerebral ventricle and in human embryonic kidney 293 (HEK293sw) cells. Daily intraperitoneal administration of HupA for 12 consecutive days produced significant reversals of the Abeta(1-40)-induced down-regulation of secretory APP (APPs) and protein kinase C (PKC) in rats. In the HEK293sw cells, the level of APPs was increased significantly with HupA treatment, and there was a similar change in PKCalpha level under the same condition. However, no significant alternations in the levels of PKCdelta and PKC were found after HupA treatment. These findings suggest that HupA may affect the processing of APP by up-regulating PKC, especially PKCalpha.
Zhang
Hai Yan
HY
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai, 201203, China.
Yan
Han
H
Tang
Xi Can
XC
D000470:Alkaloids; D016229:Amyloid beta-Peptides / Q000008:administration & dosage*; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D009154:Mutation / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage*; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000235:genetics; D051571:Protein Kinase C-alpha; D051381:Rats; D017207:Rats, Sprague-Dawley; D012717:Sesquiterpenes / Q000494:pharmacology*
D000470:Alkaloids; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D012717:Sesquiterpenes; C078592:amyloid beta-protein (1-40); C050426:huperzine A; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha