%0 Journal Article
%T Inhibition of Nuclear Nox4 Activity by Plumbagin: Effect on Proliferative Capacity in Human Amniotic Stem Cells
%A Marianna Guida
%A Tullia Maraldi
%A Elisa Resca
%A Francesca Beretti
%A Manuela Zavatti
%A Laura Bertoni
%A Giovanni B. La Sala
%A Anto De Pol
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/680816
%X Human amniotic fluid stem cells (AFSC) with multilineage differentiation potential are novel source for cell therapy. However, in vitro expansion leads to senescence affecting differentiation and proliferative capacities. Reactive oxygen species (ROS) have been involved in the regulation of stem cell pluripotency, proliferation, and differentiation. Redox-regulated signal transduction is coordinated by spatially controlled production of ROS within subcellular compartments. NAD(P)H oxidase family, in particular Nox4, has been known to produce ROS in the nucleus; however, the mechanisms and the meaning of this function remain largely unknown. In the present study, we show that Nox4 nuclear expression (nNox4) increases during culture passages up to cell cycle arrest and the serum starvation causes the same effect. With the decrease of Nox4 activity, obtained with plumbagin, a decline of nuclear ROS production and of DNA damage occurs. Moreover, plumbagin exposure reduces the binding between nNox4 and nucleoskeleton components, as Matrin 3. The same effect was observed also for the binding with phospho-ERK, although nuclear ERK and P-ERK are unchanged. Taken together, we suggest that nNox4 regulation may have important pathophysiologic effects in stem cell proliferation through modulation of nuclear signaling and DNA damage. 1. Introduction Stem cells are characterized by a high capacity of self-renewal and differentiation. Through self-renewal, stem cells maintain the homeostasis of a stem cell pool; through differentiation, stem cells can give rise to terminal cells with diverse morphology and functions [1]. In tissues, most stem cells are in the quiescent state, and they are protected by special microenvironments (niches) [2]. The quiescence of stem cells may prevent the accumulation of DNA replication errors [3] and may facilitate resistance to many stressors [4]. The intracellular ROS level is a critical factor that regulates the quiescent status of mesenchymal stem cells (MSC) [5]. Similar to the low partial pressure of oxygen, low levels of ROS in niches are important for the stemness of MSC [6]. However, in vitro expansion of stem cells implies normoxic culture condition. Indeed, MSC proliferative and colony formation capacity is significantly increased in normoxia. However, MSC expanded under normoxia show a threefold to fourfold increase in senescence, suggesting that hypoxia prevents oxidative stress-induced senescence and preserves MSC long-term self-renewal [7]. Accumulation of ROS is a common occurrence in senescent cells. Studies have shown
%U http://www.hindawi.com/journals/omcl/2013/680816/