RESUMO
Ginsenoside, the active principles in Panax ginseng root, has been demonstrated to show neurotrophic and neuroprotective actions for prevention of neuron degeneration. Deposition of beta-amyloid peptide (Abeta) causes neurotoxicity through the formation of plaques in brains with Alzheimer's disease. Pituitary adenylate cyclase-activating polypeptide (PACAP) is introduced as a neurotrophic factor to promote cell survival. However, effect of Rh2, one of ginsenosides, on PACAP expression induced by Abeta remains unclear. In the present study, we found that Rh2 stimulates PACAP gene expression and cell proliferation in type I rat brain astrocytes (RBA1) cells and both effects were not modified by the estrogen antagonists (MPP or ICI 182780). Also, Rh2 ameliorates the RBA1 growth inhibition of Abeta. Moreover, blockade of PACAP receptor PAC1 using PACAP (6-38) inhibits all the actions of Rh2. These results suggest that Rh2 can induce an increase of PACAP to activate PAC1, but not estrogen receptor, and thereby leads to attenuate Abeta-induced toxicity. Thus, ginseng seems useful in the prevention of dementia.
Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/antagonistas & inibidores , Astrócitos/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Ginsenosídeos/farmacologia , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Doença de Alzheimer/metabolismo , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/toxicidade , Animais , Animais Recém-Nascidos , Astrócitos/metabolismo , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Antagonistas de Estrogênios/farmacologia , Ginsenosídeos/uso terapêutico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/efeitos dos fármacos , Placa Amiloide/efeitos dos fármacos , Placa Amiloide/metabolismo , Placa Amiloide/patologia , Ratos , Ratos Wistar , Receptores de Estrogênio/efeitos dos fármacos , Receptores de Estrogênio/metabolismo , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/efeitos dos fármacos , Receptores de Polipeptídeo Hipofisário Ativador de Adenilato Ciclase/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/fisiologiaRESUMO
Pituitary adenylate cyclase-activating polypeptide (PACAP) is an endogenous neuropeptide observed in adrenal gland and sympathetic ganglia to regulate catecholamine synthesis and release. Both PACAP and glucocorticoid showed the activity to elevate catecholamine level through the stimulation of biosynthesis. However, the relationship of glucocorticoid and PACAP for this action is still unclear. Thus, alterations of gene expression, dopamine (DA) content, and cell proliferation in rat pheochromocytoma PC12 cells are employed as indicators to clarify this relationship in the present study. From the analysis of RT-PCR, the mRNA level of PACAP was observed to be raised by dexamethasone (DEX) and this action was blocked in cells treated with RU486 (mifepristone), a glucocorticoid receptor (GR) antagonist, or actinomycin D, a transcriptional inhibitor. An increase of DA content by HPLC analysis and/or cell proliferation identified by MTT assay by DEX was also observed which could be inhibited by PACAP (6-38) at concentration sufficient to block PACAP type 1 (PAC1) receptor. These results suggest that PACAP is involved in DEX-induced DA biosynthesis and cell proliferation in PC12 cells.
