Asymmetrical cross-talk between the endoplasmic reticulum stress and oxidative stress caused by dextrose

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• 作者：Arshag D. Mooradian ; ^{arshag.mooradian@jax.ufl.edu" class="auth_mail" title="E-mail the corresponding author} ; Luisa Onstead-Haas ; Michael J. Haas
• 关键词：Oxidative stress ; Endoplasmic reticulum stress ; Endothelial cells ; Antioxidants ; Hyperglycemia
• 刊名：Life Sciences
• 出版年：2016
• 出版时间：1 January 2016
• 年：2016
• 卷：144
• 期：Complete
• 页码：37-48
• 全文大小：1446 K

文摘

Oxidative and endoplasmic reticulum (ER) stresses are implicated in premature cardiovascular disease in people with diabetes. The aim of the present study was to characterize the nature of the interplay between the oxidative and ER stresses to facilitate the development of therapeutic agents that can ameliorate these stresses.

Main methods

Human coronary artery endothelial cells were treated with varying concentrations of dextrose in the presence or absence of three antioxidants (alpha tocopherol, ascorbate and ebselen) and two ER stress modifiers (ERSMs) (4-phenylbutyrate and taurodeoxycholic acid). ER stress was measured using the placental alkaline phosphatase assay and superoxide (SO) generation was measured using the superoxide-reactive probe 2-methyl-6-(4-methoxyphenyl)-3,7-dihydroimidazo[1,2-A]pyrazin-3-one hydrochloride chemiluminescence.

Key findings

The SO generation was increased with increasing concentrations of dextrose. The ER stress was increased with both low (0 and 2.75 mM) and high (13.75 and 27.5 mM) concentrations of dextrose. The antioxidants inhibited the dextrose induced SO production while in high concentrations they aggravated ER stress. The ERSM reduced ER stress and potentiated the efficacy of the three antioxidants. Tunicamycin-induced ER stress was not associated with increased SO generation. Time course experiments with a high concentration of dextrose or by overexpressing glucose transporter one in endothelial cells revealed that dextrose induced SO generation undergoes adaptive down regulation within 2 h while the ER stress is sustained throughout 72 h of observation.

Significance

The nature of the cross talk between oxidative stress and ER stress induced by dextrose may explain the failure of antioxidant therapy in reducing diabetes complications.