Peroxisome dynamics and regulation by ROS and

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... Feb 3;147(3):301-11 FCT. (P2020-PTDC/DTP-FTO/5651/2014); CT/ MEC and FEDER (PT2020/UID/01/. 0145/FERDER/007728; N-01–0145-FEDER-000024).
A. Stepanova et al. / Free Radical Biology and Medicine 120 (2018) S45–S166

may enhance sterilization by increasing the ROS productive ability from PMN in the oral cavity.

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Faculdade de Ciências da Universidade do Porto, ICBAS, Porto, Portugal

E-mail address: [email protected] http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.384

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Peroxisome dynamics and regulation by ROS and pexophagy in response to Cd stress Calero Nieves 1, Manuel Fernández Alejandro 1, Maria Rodriguez-Serrano 1, Ana M. Laureano-Marin 2, Marino Exposito 3, Philip Mullineaux 3, Cecilia Gotor 2, Maria C. Romero-Puertas 1, Adela Olmedilla 1, Luisa M. Sandalio 1

The endocannabinoid system (ECS) regulates several reproductive events such as decidualization, implantation and placentation. Placental development involves a balance between proliferation, differentiation and cell death of trophoblasts. We have reported that 2-AG induces apoptosis in trophoblast cells [1], on which endoplasmic reticulum (ER)-stress might play a role. Prolonged ER-stress may activate pancreatic ER kinase (PERK) protein and trigger apoptotic pathways. Therefore, in this work it was evaluated the role of PERK branch on 2-AG induced-apoptosis in BeWo cell line, a model of cytotrophoblasts. Through q-PCR it was observed that 2-AG increased mRNA levels of crucial ERstress markers: CHOP and ATF4. Through Western-blot we found that 2-AG also increased CHOP protein levels and activation/phospohorylation of eIF2α. The involvement of cannabinoid receptors was also investigated. Herein we found that 2-AG induced apoptosis is mediated by activation of PERK branch of ER-stress response which may impair placental development, and lead to miscarriage, fetal growth-restriction and pregnancy-related diseases.

E-mail address: [email protected]

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Dept. of Biochemistry and Cellular and Molecular Biology of Plants, EEZ-CSIC, Granada, Spain 2 Institute of Plant Biochemistry and Photosynthesis CSIC and University of Seville, Spain 3 School of Biological Sciences, University of Essex, Colchester, UK

References and Acknowledgements [1] Costa MA et al. Reproduction. 2014 Feb 3;147(3):301-11 FCT (P2020-PTDC/DTP-FTO/5651/2014); CT/ MEC and FEDER (PT2020/UID/01/ 0145/FERDER/007728; N-01–0145-FEDER-000024)

http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.386 Peroxisomes, which are highly dynamic and metabolically active organelles, play an important role in cellular functions, including reactive oxygen species (ROS) metabolism. In this study, we show that treatment of Arabidopsis plants with cadmium (Cd) produces peroxisomal extensions called peroxules and further proliferation of peroxisomes, which return to normal numbers after 24 h of treatment. Peroxule formation is mainly regulated by RBOH-dependent ROS production. To determine whether peroxisome abundance is regulated by selective autophagy (pexophagy), we performed a time course analysis of autophagy-related ATG8 proteins and genes and simultaneously imaged peroxisomes and autophagosomes in Arabidopsis plants expressing CFP-SKL and ATG8-GFP. We studied if pexophagy is regulated by ROS by analyzing carbonyl groups and peroxisomal redox state, using the specific biosensor HyperAs, as well as Arabidopsis lines with disturbances in ROS production associated with peroxisomal glycolate oxidase and RBOHs. Our results suggest that peroxules participate in stress perception and that pexophagy is significantly involved in cell responses to environmental cues regulating peroxisomal populations.

E-mail address: [email protected] Acknowledgements Funded by the Spanish MEIC-FEDER (BIO2015–67657-P) and TRANSAUTOPHAGY COST (OC-2015-1-19840)

http://dx.doi.org/10.1016/j.freeradbiomed.2018.04.385

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Underpinning the endocannabinoid 2-AG inducedapoptosis in trophoblast cells: the role of oxidative stress Marta Almada 1, João Maia 1, Sara Pereira 2, Bruno Fonseca 1, Natercia Teixeira 1, Georgina Correia-da-Silva 1 1

Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto, UCIBIO-REQUIMTE, Porto, Portugal

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Beneficial impact of a manganese(III) porphyrin in cancer cell migration Nuno Saraiva 1, Ana Flóridol 1,2, João Costa 1, Maddy Parsons 3, Ines Batinic-Haberle 4, Joana Paiva Miranda 2, Matilde Castro 2, Nuno Guerreiro Oliveira 2, Ana Sofia Fernandes 1 1

CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Lisbon, Portugal 2 Research Institute for Medicines (iMed.ULisboa), Fac. of Pharmacy, Universidade de Lisboa, Lisbon, Portugal 3 Randall Division of Cell and Molecular Biophysics, King's College London, UK 4 Department of Radiation Oncology, Duke University Medical School, Durham, NC, USA

Manganese(III) porphyrins (MnPs) mimic superoxide dismutase, scavenge different reactive species (RS) and modulate redox signaling. MnPs are currently in clinical trials in patients submitted to chemo- or radiotherapy, due to their ability to boost anticancer treatments while protecting off-target tissues. Although RS are implicated in the metastatic process, only scarce studies have addressed the impact of MnPs in metastases. Herein we characterized the impact of non-cytotoxic levels of an MnP (MnTnHex-2-PyP5þ) in metastases-related processes. In renal cancer cells 786-O, MnP (0.25 mM) decreased chemotaxis. This MnP (5 μM) was also studied in MCF7 and MDA-MB-231 breast cancer cells alone and in combination with doxorubicin (dox; 0.1 μM). The co-treatment decreased the collective motility of MCF7, the chemotactic migration of both cell lines, and the proteolytic invasion of MDA-MB-231 cells. MnP also counteracted the increase in random MDA-MB-231 cell migration induced by dox. To explore the underlying mechanisms, the effects in cell spread/area, focal adhesions, intracellular RS levels, and NFkB activity were studied. Our results suggest that MnP may have a beneficial impact in reducing cancer cells migration and warrant further studies regarding MnP-based anticancer approaches.