Oxidative stress promotes the increase of matrix metalloproteinases-2 and -9 activities in the feto-placental unit of diabetic rats

Abstract

Maternal diabetes increases the risk of congenital malformations, placental dysfunction and diseases in both the neonate and the offspring's later life. Oxidative stress has been involved in the etiology of these abnormalities. Matrix metalloproteases (MMPs), involved in multiple developmental pathways, are increased in the fetus and placenta from diabetic experimental models. As oxidants could be involved in the activation of latent MMPs, we investigated a putative relationship between MMPs activities and oxidative stress in the feto-placental unit of diabetic rats at midgestation. We found that H2O2 enhanced and that superoxide dismutase (SOD) reduced MMPs activities in the maternal side of the placenta and in the fetuses from control and diabetic rats. MMPs were not modified by oxidative status in the fetal side of the placenta. Lipid peroxidation was enhanced in the maternal and fetal sides of the placenta and in the fetus from diabetic rats when compared to controls, and gradually decreased from the maternal placental side to the fetus in diabetic animals. The activities of the antioxidant enzymes SOD and catalase were decreased in the maternal placental side, catalase activity was enhanced in the fetal placental side and both enzymes were increased in the fetuses from diabetic rats when compared to controls. Our data demonstrate changes in the oxidative balance and capability of oxidants to upregulate MMPs activity in the feto-placental unit from diabetic rats, a basis to elucidate links between oxidative stress and alterations in the developmental pathways in which MMPs are involved.

Ascorbic Acid Reduces the Adverse Effects of Delayed Administration of Tissue Plasminogen Activator in a Rat Stroke Model

“…Matrix metalloproteinases are involved in the pathogenesis of several brain diseases that share common pathophysiological processes such as BBB disruption, oxidative stress and inflammation [16]. Oxidative stress was not directly studied in this report, and this is a limitation of our study; however, there are significant correlations between oxidative stress and MMP-9 in both stroke patients and animals [29,30]. In stroke patients, oxidative stress has been shown to have a significant correlation with MMP-9 expression [29].…”

Melatonin inhibits IL1β-induced MMP9 expression and activity in human umbilical vein endothelial cells by suppressing NF-κB activation

“…MMP9 is activated by reactive oxygen species and its expression is likely to be regulated by oxidative stress (Rajagopalan et al 1996, Mori et al 2004, Pustovrh et al 2005. Studies in the literature indicate that melatonin significantly inhibits the translocation and binding of NF-kB to DNA in rat spleen and downregulates the expression of NF-kB/p65 in the pathophysiology of ischemia/reperfusion injury in a model of rat kidney transplantation (Chuang et al 1996, Li et al 2009).…”

Upregulation of equine matrix metalloproteinase 1 by bovine papillomavirus type 1 is through the transcription factor activator protein-1

“…Activator protein-1 (AP-1) is the key cellular factor involved in regulation of MMP expression (Lin et al, 1993). Extracellular stimuli including growth factors, cytokines, stress and virus infection can induce MMP expression (Hirata et al, 2003;Lichtinghagen et al, 2003;Pustovrh et al, 2005 We have previously shown that BPV-1 upregulates MMP-1 expression and activity and is essential for the transformation of sarcoid fibroblasts, including invasiveness (Yuan et al, 2008b(Yuan et al, , 2010a. However, it remains unclear how BPV-1 proteins regulate MMP-1 expression.…”