Corrigendum to "European contribution to the study of ROS:A summary of the findings and prospects for the future from the COST action BM1203 (EU-ROS)" [Redox Biol. 13 (2017) 94-162]

The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed

Potential biological role of poly (ADP-ribose) polymerase (PARP) in male gametes

Maintaining the integrity of sperm DNA is vital to reproduction and male fertility. Sperm contain a number of molecules and pathways for the repair of base excision, base mismatches and DNA strand breaks. The presence of Poly (ADP-ribose) polymerase (PARP), a DNA repair enzyme, and its homologues has recently been shown in male germ cells, specifically during stage VII of spermatogenesis. High PARP expression has been reported in mature spermatozoa and in proven fertile men. Whenever there are strand breaks in sperm DNA due to oxidative stress, chromatin remodeling or cell death, PARP is activated. However, the cleavage of PARP by caspase-3 inactivates it and inhibits PARP's DNA-repairing abilities. Therefore, cleaved PARP (cPARP) may be considered a marker of apoptosis. The presence of higher levels of cPARP in sperm of infertile men adds a new proof for the correlation between apoptosis and male infertility. This review describes the possible biological significance of PARP in mammalian cells with the focus on male reproduction. The review elaborates on the role played by PARP during spermatogenesis, sperm maturation in ejaculated spermatozoa and the potential role of PARP as new marker of sperm damage. PARP could provide new strategies to preserve fertility in cancer patients subjected to genotoxic stresses and may be a key to better male reproductive health

Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy. © 2019 John Wiley & Sons Lt

HN1 negatively influences the ß-catenin/E-cadherin interaction, and contributes to migration in prostate cells

PubMed ID: 25169422Previously, it has been reported that HN1 is involved in cytoplasmic retention and degradation of androgen receptor in an AKT dependent manner. As HN1 is a hormone inducible gene, and has been shown that it is upregulated in various cancers, we studied the importance of HN1 function in ß-catenin signaling in prostate cancer cell line, PC-3 and mammary cancer cell line MDA-MB231. Here, we demonstrated that HN1 physically associates with GSK3ß/ß-catenin destruction complex and abundantly localizes to cytoplasm, especially when the GSK3ß is phosphorylated on S9 residue. Further, ectopic HN1 expression results an increase in the ß-catenin degradation leading to loss of E-cadherin interaction, concurrently contributing to actin re-organization, colony formation and migration in cancer cell lines. Thus, we report that HN1 is an essential factor for ß-catenin turnover and signaling, augments cell growth and migration in prostate cancer cells. © 2014 Wiley Periodicals, Inc

Ubiquitously expressed hematological and neurological expressed 1 downregulates Akt-mediated GSK3ß signaling, and its knockdown results in deregulated G2/M transition in prostate cells

PubMed ID: 21323578As the molecular mechanism of ß-catenin deregulation is not well understood, and stabilized ß-catenin is known to translocate into the nucleus and activate genes for proliferation, a novel regulatory factor, hematological and neurological expressed 1 (HN1), for Akt-GSK3ß-ß- catenin axis is reported here. In our studies, HN1 gene structure was characterized. HN1 expression was found to be epidermal growth factor-responsive in PC-3 cells, and protein expression was also upregulated in PC-3 and LNCaP but not in DU145 cells. Additionally, HN1 was found to be downregulated by the specific AKT inhibitor wortmannin but not with PI3K or MAPK inhibitors, LY294002 and PD98059, respectively, in PC-3 and MCF-7 cells. Further, siRNA-mediated knockdown of HN1 resulted in considerable increase in Akt (S473) and GSK3ß (S9),(Y216) phosphorylations; moreover, subsequent accumulation of ß-catenin, increase in c-myc expression, and nuclear accumulation of cyclin D1 were observed in PC-3 cells. Knockdown of HN1 also resulted in prolongation of G 1 phase in cell cycle, increasing tetraploidy, presumably because of cells escaping from abnormal mitosis in PC-3 cells. Consistently, overexpression of HN1 reversed the cell-cycle-specific observations, resulted in accumulation of cells in G 2/M, and reduced the proliferation rate, which were investigated using flow cytometry and methylthiazol tetrazolium assays. As activating mutations of ß-catenin have been demonstrated in late-stage tumors, and ß-catenin stabilization was correlated with poor prognosis in previous reports, epidermal growth factor-upregulated HN1 expression might have a role in deregulating the AKT-GSK3ß (S9)-mediated signaling as a novel compensating mechanism. © 2011 Mary Ann Liebert, Inc