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1.
Biochem Biophys Res Commun ; 402(1): 42-7, 2010 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-20888794

RESUMEN

Wogonin is a flavonoid isolated from Scutellaria baicalensis root, and has multiple pharmacological effects, including anti-inflammatory, anti-oxidant, and anti-cancer effects. It is also neuroprotective in the brain under many stress conditions, but wogonin does not elevate neuronal cell survival. Thus, the mechanisms controlling the neuroprotective effect of wogonin are not clear. Neural precursor cells (NPCs), present in the hippocampus and subventricular zone of adult brains, replace damaged cells. In this study we investigated the biological functions underlying the neuroprotective effect of wogonin on NPCs. We initially examined survival of NPCs but found it was slightly reduced at concentrations higher than 2µg/ml. When we explored differentiation of NPCs into neuronal cells, the number of differentiated cells expressing neurofilaments was increased remarkably (fourfold) in the hippocampal NPCs treated with wogonin. Wogonin maximally elevated the expressions of presynaptic protein, synapsin I and postsynaptic protein (PSD95) at a concentration of 0.7µg/ml. Differentiated cells containing longer neurites were significantly increased in cortical NPCs, primarily cultured from rat E14 embryonic brain. Wogonin also promoted differentiation of NPCs into mature neurons in vivo. When transplanted into the adult rat hippocampus, NPCs differentiated into cells expressing NeuN, the mature neuron marker, by 4weeks after transplantation. These data indicate that wogonin induces differentiation of NPCs both in culture and in vivo, and suggest that facilitation of NPC differentiation is a biological activity by which wogonin protects neurons in damaged brain.


Asunto(s)
Flavanonas/farmacología , Células-Madre Neurales/efectos de los fármacos , Neuritas/efectos de los fármacos , Neurogénesis , Animales , Células Cultivadas , Células Madre Embrionarias/citología , Células Madre Embrionarias/efectos de los fármacos , Hipocampo/citología , Hipocampo/efectos de los fármacos , Masculino , Células-Madre Neurales/fisiología , Células-Madre Neurales/trasplante , Neuritas/fisiología , Ratas , Ratas Endogámicas , Trasplante de Células Madre
2.
Neuroreport ; 18(12): 1225-9, 2007 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-17632272

RESUMEN

Amyloid precursor protein generates the secreted amyloid precursor protein alpha, which protects hippocampal neurons from ischemic injury and facilitates neuronal survival and synaptogenesis in the developing nervous system. Here, we examined whether platelet-derived growth factor regulates the generation of secreted amyloid precursor protein alpha during the neuronal differentiation of hippocampal precursor cells, HiB5. We showed that platelet-derived growth factor promoted amyloid precursor protein production and secreted amyloid precursor protein alpha secretion. These effects of platelet-derived growth factor were diminished by the PI3K-specific inhibitor wortmannin and the protein kinase C-specific inhibitor GF109203X, suggesting the involvement of the PI3K and protein kinase C-signaling pathway. Furthermore, the conditioned media enriched with secreted amyloid precursor protein alpha promoted the survival of HiB5 cells during neuronal differentiation. These results suggest that the neurotrophic effect of platelet-derived growth factor is mediated in part via upregulation of the expression and release of secreted amyloid precursor protein alpha.


Asunto(s)
Precursor de Proteína beta-Amiloide/metabolismo , Diferenciación Celular/fisiología , Hipocampo/embriología , Neuronas/metabolismo , Factor de Crecimiento Derivado de Plaquetas/metabolismo , Células Madre/metabolismo , Precursor de Proteína beta-Amiloide/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Línea Celular , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/fisiología , Medios de Cultivo Condicionados/farmacología , Inhibidores Enzimáticos/farmacología , Hipocampo/citología , Hipocampo/efectos de los fármacos , Humanos , Neuronas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Factor de Crecimiento Derivado de Plaquetas/farmacología , Proteína Quinasa C/antagonistas & inhibidores , Proteína Quinasa C/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Células Madre/efectos de los fármacos , Regulación hacia Arriba/efectos de los fármacos , Regulación hacia Arriba/fisiología
3.
FASEB J ; 16(10): 1310-2, 2002 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-12154005

RESUMEN

Junctin is a 26-kDa integral membrane protein, colocalized with the ryanodine receptor (RyR) and calsequestrin at the junctional sarcoplasmic reticulum (SR) membrane in cardiac and skeletal muscles. To elucidate the functional role of junctin in heart, transgenic (TG) mice overexpressing canine junctin (24-29 folds) under the control of mouse a-myosin heavy chain promoter were generated. Overexpression of the junctin in mouse heart was associated with heart enlargements, bradycardia, atrial fibrillation, and increased fibrosis. Many ultrastructural alterations were observed in TG atria. The junctional SR cisternae facing transverse-tubules contained a dense matrix of calsequestrin in TG heart. According to echocardiography, TG mice showed enlarged left ventricles, dilated right atriums, and ventricles with paradoxical septal motion and impaired left ventricular systolic function. Overexpression of junctin led to down-regulation of triadin and RyR but to up-regulation of dihydropyridine receptor. The L-type Ca2+ current density and action potential durations increased, which could be the cause for the bradycardia in TG heart. This study provides an important example of pathogenesis leading to substantial cardiac remodeling and atrial fibrillation, which was caused by overexpression of junctin in heart.


Asunto(s)
Fibrilación Atrial/etiología , Fibrilación Atrial/patología , Proteínas de Unión al Calcio , Cardiomegalia/etiología , Proteínas Portadoras/genética , Proteínas de la Membrana , Oxigenasas de Función Mixta , Proteínas Musculares/genética , Potenciales de Acción , Animales , Fibrilación Atrial/fisiopatología , Bradicardia/etiología , Canales de Calcio Tipo L/fisiología , Cardiomegalia/patología , Cardiomegalia/fisiopatología , Proteínas Portadoras/metabolismo , Células Cultivadas , Conductividad Eléctrica , Fibrosis , Corazón/fisiopatología , Cinética , Ratones , Ratones Transgénicos , Modelos Cardiovasculares , Contracción Muscular , Proteínas Musculares/metabolismo , Miocardio/patología , Miocardio/ultraestructura , Remodelación Ventricular
4.
Biomaterials ; 30(1): 126-32, 2009 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-18838157

RESUMEN

In this study, we tested the hypothesis that the amount of nerve growth factor (NGF) required for pheochromocytoma (PC12) cell culture can be dramatically reduced by controlled release of NGF from a collagen gel coating on the culture surface. Cells were cultured on collagen gels loaded with various amounts of NGF. As a control, PC12 cells were cultured on collagen gels with daily addition of various amounts of NGF to the culture medium. After an initial 12h burst, NGF was steadily released from the gels for 4 days. Apoptotic activity and cell viability were determined using terminal uridine nick end labeling and the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, respectively. Neuronal differentiation was determined using immunocytochemistry and Western blot analysis. Compared to 100 ng NGF daily addition (300 ng over 3 days), 1 ng NGF daily addition showed dramatically decreased cell viability and neuronal differentiation and increased apoptotic activity. In contrast, collagen gels loaded with 10 ng NGF yielded cell viability, apoptotic activity, and neuronal differentiation similar to those of culture with 100 ng NGF daily addition. Our method reduced the amount of NGF required for PC12 cell culture to 1/3th of that used in daily addition without affecting cell viability, apoptosis, or differentiation. This method could economize large-scale culture of stem cells by reducing the amount of costly growth factors needed.


Asunto(s)
Colágeno/metabolismo , Factor de Crecimiento Nervioso/farmacología , Neuronas/citología , Neuronas/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Western Blotting , Diferenciación Celular/efectos de los fármacos , Forma de la Célula/efectos de los fármacos , Medios de Cultivo , Geles , Cinética , Mitocondrias/metabolismo , Neuritas/efectos de los fármacos , Neuritas/metabolismo , Neuronas/metabolismo , Células PC12 , Ratas , Propiedades de Superficie/efectos de los fármacos
5.
J Biomater Sci Polym Ed ; 18(2): 223-39, 2007.
Artículo en Inglés | MEDLINE | ID: mdl-17323855

RESUMEN

The biocompatibility of polymer scaffolds as neural stem cell transplantation matrices has not yet been studied extensively. In this study, we evaluated the biocompatibility of various biodegradable polymers for neural stem cells. The biocompatibility tests were performed by culturing hippocampal progenitor cells (HiB5) on films of poly(lactic-co-glycolic acid) (PLGA), poly(L-lactide-co-epsilon-caprolactone) (PLCL) and poly(L-lactic acid) (PLLA) or in the presence of extracts from these polymers. Specifically, the viability, mitochondrial metabolic activity, proliferation, apoptosis and neurite out-growth of HiB5 cells were examined in biocompatibility tests. Among the tested polymers, PLGA performed best with respect to cell viability, mitochondrial metabolic activity and apoptotic activity. Compared to the other polymers, PLLA showed the worst results in all categories evaluated. PLGA also showed favorable results for neurite out-growth of HiB5 cells. The results of this study demonstrate the promising biocompatibility of PLGA as a scaffold for neural stem cell transplantation for nerve regeneration.


Asunto(s)
Materiales Biocompatibles , Neuronas/citología , Células Madre/citología , Animales , Apoptosis , Diferenciación Celular , Línea Celular , Proliferación Celular , Hipocampo/citología , Ácido Láctico , Ensayo de Materiales , Regeneración Nerviosa , Neuronas/metabolismo , Poliésteres , Ácido Poliglicólico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Polímeros , Ratas , Trasplante de Células Madre , Células Madre/metabolismo , Ingeniería de Tejidos
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