Pigment-Epithelium Derived Factor (PEDF) and the human ovary: A role in the generation of ROS in granulosa cells

Pigment epithelium-derived factor stimulates skeletal muscle glycolytic activity through NADPH oxidase-dependent reactive oxygen species production

“…PEDF has emerged as a potent inducer of ROS in human ovary [Kampfer et al 2014]. This is in agreement with our data where PEDF exposure induced ROS generation in skeletal myocytes and such an effect was ablated by co-treatment with antioxidants such as catalase and superoxide dismutase.…”

“…Accumulating evidence suggests that PEDF is a stress inducing protein that induces inflammatory signalling in peripheral tissues, increases adipocyte lipolysis and promotes lipid accumulation in muscle and liver [Famulla et al 2011, Crowe et al 2009. Recently, PEDF emerged as an ovarian factor involved in the generation of ROS [Kampfer et al 2014]. Hence, we intended to explore if PEDF impacts ROS generation and any associated metabolic effects in skeletal muscle, which is the major site of peripheral glucose and amino acid metabolism.…”

“…Employing the mito-stress test in C2C12 using extracellular flux analysis, PEDF did not cause any measurable mitochondrial stress in C2C12 and our results are in agreement with studies conducted by Borg et al 2011, where PEDF did not impact mitochondrial function when isolated from mouse muscle. This prompted us to look into the other major ROS sources in skeletal muscle which includes NOX, the inhibition of which attenuated PEDF-induced ROS and this is similar to the effect of PEDF in human ovarian cells where PEDF-induced ROS production was demonstrated to be NOX-dependent[Kampfer et al 2014]. Other studies have shown that PLA2 regulates NOX[Zaho et al 2002] …”

“…[Matono et al 2014]. Recently, PEDF has emerged as a likely factor that could contribute to ROS homeostasis and ovarian oxidative stress [Kampfer et al 2014]. In this study, we sought to explore if PEDF could impact ROS production and ROS-dependent metabolic alterations in skeletal muscle cells.…”

Role of pigment epithelium-derived factor in the reproductive system

“…As in other tissues, we have further demonstrated that the expression of PEDF is inverse to that of VEGF; human chorionic gonadotropin (hCG) causes a decrease in the expression of PEDF and an increase in the expression of VEGF, both in vivo and in vitro (Chuderland et al 2013a). We and others have shown that granulosa cells express PEDF-R N (Kampfer et al 2014) and that in vitro stimulation with rPEDF downregulates VEGF mRNA synthesis in a dosedependent manner (Chuderland et al 2013a). The direct in vitro effect of rPEDF on VEGF biosynthesis in granulosa cells suggests that PEDF, produced by granulosa cells, exerts its effects in an autocrine or/and paracrine fashion.…”