Protective Effect of NO2-OA on Oxidative Stress, Gliosis, and Pro-Angiogenic Response in Muller Glial Cells

卷:12

Article

关键词: NITRO-FATTY ACIDS;    CONJUGATED LINOLEIC-ACID;    PREGNANCY ZONE PROTEIN;    MURINE MODEL;    NRF2;    EXPRESSION;    RETINOPATHY;    ALPHA(2)-MACROGLOBULIN;    TRANSCRIPTION;    INHIBITION;   

DOI  :  10.3390/cells12030494

来源: SCIE

【 摘 要 】

Inflammation and oxidative and nitrosative stress are involved in the pathogenesis of proliferative retinopathies (PR). In PR, a loss of balance between pro-angiogenic and anti-angiogenic factors favors the secretion of vascular endothelial growth factor (VEGF). This vascular change results in alterations in the blood-retinal barrier, with extravasation of plasma proteins such as alpha(2)-macroglobulin (alpha M-2) and gliosis in Muller glial cells (MGCs, such as MIO-M1). It is well known that MGCs play important roles in healthy and sick retinas, including in PR. Nitro-fatty acids are electrophilic lipid mediators with anti-inflammatory and cytoprotective properties. Our aim was to investigate whether nitro-oleic acid (NO2-OA) is beneficial against oxidative stress, gliosis, and the pro-angiogenic response in MGCs. Pure synthetic NO2-OA increased HO-1 expression in a time- and concentration-dependent manner, which was abrogated by the Nrf2 inhibitor trigonelline. In response to phorbol 12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS), NO2-OA prevented the ROS increase and reduced the gliosis induced by alpha M-2. Finally, when hypoxic MGCs were incubated with NO2-OA, the increase in VEGF mRNA expression was not affected, but under hypoxia and inflammation (IL-1 beta), NO2-OA significantly reduced VEGF mRNA levels. Furthermore, NO2-OA inhibited endothelial cell (BAEC) tubulogenesis. Our results highlight NO2-OA's protective effect on oxidative damage, gliosis; and the exacerbated pro-angiogenic response in MGCs.