Oxidative stress promotes proliferation and dedifferentiation of retina glial cells in vitro

Abstract

Oxidative damage is involved in triggering neuronal death in several retinal neurodegenerative diseases. The recent finding of stem cells in the retina suggests that both preventing neuronal death and replacing lost neurons might be useful strategies for treating these diseases. We have previously shown that oxidative stress induces apoptosis in cultured retinal neurons. We now investigated the response of Müller cells, proposed as retina stem cells, to this damage. Treatment of glial cell cultures prepared from rat retinas with the oxidant paraquat (PQ) did not induce glial cell apoptosis. Instead, PQ promoted their rapid dedifferentiation and proliferation. PQ decreased expression of a marker of differentiated glial cells, simultaneously increasing the expression of smooth muscle actin, shown to increase with glial dedifferentiation, the levels of cell-cycle markers, and the number of glial cells in the cultures. In addition, glial cells protected neurons in coculture from apoptosis induced by PQ and H(2)O(2). In pure neuronal cultures, PQ induced apoptosis of photoreceptors and amacrine neurons, simultaneously decreasing the percentage of neurons preserving mitochondrial membrane potential; coculturing neurons with glial cells completely prevented PQ-induced apoptosis and preserved mitochondrial potential in both neuronal types. These results demonstrate that oxidative damage activated different responses in Müller glial cells; they rapidly dedifferentiated and enhanced their proliferation, concurrently preventing neuronal apoptosis. Glial cells might not only preserve neuronal survival but also activate their cell cycle in order to provide a pool of new progenitor cells that might eventually be manipulated to preserve retinal functionality.

Entamoeba histolytica Infection and Secreted Proteins Proteolytically Damage Enteric Neurons

“…Glial cell sparing in the presence of neuronal death has been observed in other coculture models-hydrogen peroxide or paraquat-induced oxidative damage of retinal neuroglial cocultures caused the selective death of neurons with glial cell proliferation (1). We have previously shown the selective neurotoxicity of acrylamide or hydrogen peroxide in our enteric cocultures, suggesting that neurons are especially vulnerable to oxidative conditions (23).…”

Mouse Models of Oxidative Stress Indicate a Role for Modulating Healthy Aging

“…While oxidant stress in the mitochondria may be hypothesized to have negative consequences, in the cytosol hydrogen peroxide is suggested to induce necessary redox-dependent signaling molecules [25] designed to either bolster antioxidative defenses (Keap1-NRF2 axis) [49], induce apoptosis and energy control (GSK3β [50-51], JNK [52-55], ERK-1,2 [55], p38 [55], p53 [56]), increase proliferation [57], differentiation [57], apoptosis [50-54,56] or necrosis as ascribed to glutathione redox couples [58-60]. Oxidation of the cysteine residues of many signaling molecules is important for cell signaling processes, and it has become apparent that reduced oxidative stress can impair signaling cascades for proliferation and differentiation [57].…”

Effects of different levels of dietary selenium on the proliferation of spermatogonial stem cells and antioxidant status in testis of roosters

“…The properties of SSCs including self-renewal capability and differentiation potential are modulated by a specific microenvironment called "niche", which is regulated by many complex factors (Oatley and Brinster, 2008;De Rooij, 2009). Oxidative stress related to the generation of reactive oxygen species (ROS) has also been associated with cell proliferation, differentiation and apoptosis in various systems (Dragin et al, 2006;Abrahan et al, 2009;Guo et al, 2010). Se is the catalytic center of several antioxidant enzymes and proteins such as glutathione peroxidase (GSH-Px) and selenoprotein P, some of which are involved in the regulation of oxidative microenvironment (Rotruck et al, 1973;Carlson et al, 2009;Wayne and Zeynep, 2010;Li et al, 2012).…”