Effects on Oxidative Adaptive Response and Signal Transduction Pathway in Vascular Endothelial Cell (SVEC4-10) Exposed to Arsenic under High Glucose Condition

Autor: Chu, Chih-Hsuan, 朱芷萱
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 103
Arsenic is a naturally occurring and poisonous metalloid element that exists in environmental sources such as air, water, and soil. Endothelial cell toxicity is known that can directly cause endothelial injury and apoptosis. Blackfoot disease is the peripheral vascular disease. The previous studies have shown that blackfoot disease hyperendemic area resident exposed to high level of arsenic in Taiwan and Bangladesh may relate to the development of diabetes. To clarify the molecular mechanisms through which arsenic causes injuries to blood vessels under high glucose condition, SV40 transformation of lymphatic endothelial cells (SVEC4-10) were used to expose to different concentration of arsenic under high glucose (80 mM) condition, and analyzed the oxidative adaptive response in blood vessels and the signal pathway involved in the SVEC4-10 cells. The cells were incubated with different concentrations of arsenic and high glucose (80 mM) for 24 hr, the percentage of cell death was in dose- and time-dependent. It could decrease the mitochondrial membrane potential, and increased the oxidative marker 2-thiobarbituric acid-reactive substances (TBARS) and reactive oxygen species (ROS) production. Arsenic and high glucose would let the cell cycle arrest in G2 phase and change the expression of antioxidant enzyme superoxide dismutase (SOD). Selective blocking of the mitogen-activated protein kinase (MAPK) pathways with c-Jun N-terminal kinase (JNK) inhibitor SP600125 and extracellular signal-regulated kinase (ERK) inhibitor U0126 could significantly decrease arsenic-induced cell death under the high glucose condition. Treatment with arsenic also triggered the expression of endoplasmic reticulum (ER) stress marker, glucose-regulated protein (GRP78) under high glucose conditions. These results showed that oxidative stress and ER stress may be associated with arsenic-induced cytotoxicity under high glucose condition. The assays indicated that arsenic treatment under high glucose condition induced oxidative stress through JNK/ERK pathway in SVEC4-10 cells. The results suggest that arsenic and high glucose may have synergistic effect.
Databáze: Networked Digital Library of Theses & Dissertations