Role of endoplasmic reticular stress in aortic endothelial apoptosis induced by intermittent/persistent hypoxia / 中华医学杂志(英文版)
Chin. med. j
; Chin. med. j;(24): 4517-4523, 2013.
Article
en En
| WPRIM
| ID: wpr-327538
Biblioteca responsable:
WPRO
ABSTRACT
<p><b>BACKGROUND</b>Accumulated evidence shows that hypoxia can induce endothelial apoptosis, however the mechanism is still unknown. We hypothesized whether intermittent or persistent hypoxia could induce endoplasmic reticular stress, leading to endothelial apoptosis.</p><p><b>METHODS</b>Twenty-four 8-week male Sprague Dawley (SD) rats were divided into three groups: normoxia (NC) group, intermittent hypoxia (IH) group and persistent hypoxia (PH) group. TUNEL staining was performed to detect aortic arch endotheliar apoptosis, and immunohistochemistry for BIP, CHOP and caspase12 to test protein expression; human umbilical vein endothelial cells (HUVECs) of the line ECV304 were cultured (with or without taurodeoxycholic acid (TUDCA) 10 mmol/L, 100 mmol/L) and divided into four groups: NC group (20.8% O2 for 4 hours), PH1 group (5% O2 for 4 hours), PH2 group (5% O2 for 12 hours) and IH group (20.8% O2 and 5% O2 alternatively for 8 hours). Annexin V-fluorescein-isothiocyanate/propidium iodide flow cytometry was used to assess apoptosis in each group. The expressions of GRP78, CHOP and caspase12 were detected by real-time quantitative reverse-transcription PCR. Result Intermittent and persistent hypoxia could increase the rate of endothelium apoptosis and the expressions of GRP78, CHOP and caspase12 compared with the control, induction by intermittent hypoxia was slightly higher than persistent hypoxia. In the HUVEC experiment, TUDCA significantly reduced apoptosis and the expressions of GRP78, CHOP and caspase12.</p><p><b>CONCLUSION</b>Hypoxia, especially intermittent, can induce endothelial cell apoptosis possibly through endoplasmic reticulum stress pathway, which can be attenuated by taurodeoxycholic acid.</p>
Texto completo:
1
Base de datos:
WPRIM
Asunto principal:
Farmacología
/
Fisiología
/
Ácido Taurodesoxicólico
/
Ratas Sprague-Dawley
/
Apoptosis
/
Factor de Transcripción CHOP
/
Caspasa 12
/
Células Endoteliales de la Vena Umbilical Humana
/
Estrés del Retículo Endoplásmico
/
Genética
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Chin. med. j
Año:
2013
Tipo del documento:
Article