Search results for "AUTOPHAGY"
showing 10 items of 322 documents
Synthetic lethal metabolic targeting of cellular senescence in cancer therapy.
2013
Activated oncogenes and anticancer chemotherapy induce cellular senescence, a terminal growth arrest of viable cells characterized by S-phase entry-blocking histone 3 lysine 9 trimethylation (H3K9me3). Although therapy-induced senescence (TIS) improves long-term outcomes, potentially harmful properties of senescent tumour cells make their quantitative elimination a therapeutic priority. Here we use the Eµ-myc transgenic mouse lymphoma model in which TIS depends on the H3K9 histone methyltransferase Suv39h1 to show the mechanism and therapeutic exploitation of senescence-related metabolic reprogramming in vitro and in vivo. After senescence-inducing chemotherapy, TIS-competent lymphomas but …
BCL-xL, a Mitochondrial Protein Involved in Successful Aging: From C. elegans to Human Centenarians
2020
B-Cell Lymphoma-extra-large (BCL-xL) is involved in longevity and successful aging, which indicates a role for BCL-xL in cell survival pathway regulation. Beyond its well described role as an inhibitor of apoptosis by preventing cytochrome c release, BCL-xL has also been related, indirectly, to autophagy and senescence pathways. Although in these latter cases, BCL-xL has dual roles, either activating or inhibiting, depending on the cell type and the specific conditions. Taken together, all these findings suggest a precise mechanism of action for BCL-xL, able to regulate the crosstalk between apoptosis, autophagy, and senescence, thus promoting cell survival or cell death. All three pathways…
Interleukin 13 (IL-13)-regulated expression of the chondroprotective metalloproteinase ADAM15 is reduced in aging cartilage
2020
Objective The adamalysin metalloproteinase 15 (ADAM15) has been shown to protect against development of osteoarthritis in mice. Here, we have investigated factors that control ADAM15 levels in cartilage. Design Secretomes from wild-type and Adam15−/− chondrocytes were compared by label-free quantitative mass spectrometry. mRNA was isolated from murine knee joints, either with or without surgical induction of osteoarthritis on male C57BL/6 mice, and the expression of Adam15 and other related genes quantified by RT-qPCR. ADAM15 in human normal and osteoarthritic cartilage was investigated similarly and by fluorescent immunohistochemistry. Cultured HTB94 chondrosarcoma cells were treated with …
The synergistic effect of SAHA and parthenolide in MDA-MB231 breast cancer cells
2014
Abstract: The sesquiterpene lactone Parthenolide (PN) exerted a cytotoxic effect on MDA-MB231 cells, a triple-negative breast cancer (TNBC) cell line, but its effectiveness was scarce when employed at low doses. This represents an obstacle for a therapeutic utilization of PN. In order to overcome this difficulty we associated to PN the suberoylanilide hydroxamic acid (SAHA), an histone deacetylase inhibitor. Our results show that SAHA synergistically sensitized MDA-MB231 cells to the cytotoxic effect of PN. It is noteworthy that treatment with PN alone stimulated the survival pathway Akt/mTOR and the consequent nuclear translocation of Nrf2, while treatment with SAHA alone induced autophagi…
Autophagy is related to apoptosis in sea urchin embryos exposed to cadmium
2014
The sea urchin embryo is a suitable model system that offers an excellent opportunity to investigate different defense strategies activated in stress conditions. We previously showed that cadmium treatment provokes the accumulation of metal in dose-time dependent manner in embryonic cells and the activation of defense systems, such as the synthesis of HSPs and/or the initiation of apoptosis. Analyzing autophagy, by neutral red, acridine orange and LC3-detection, we demonstrated that Cd-exposed embryos adopt this process as an additional stratagem to safeguard the developmental program. We observed that embryos treated with subletal Cd concentration activate massive autophagic response after…
The autophagic demand during oogenesis and early development of sea urchin
2015
The autophagic pathway is an evolutionarily conserved homeostatic process, responsible for degradation and recycling of long-term proteins and cytoplasmic organelles in eukaryotic cells. This process constitutively occurs at basal levels and is involved in cell survival. Increased autophagy is induced by environmental cues, such as starvation and many stress agents, while excessive levels of autophagy can lead to autophagic Programmed Cell Death, with features that differ from those of the apoptotic process. We recently demonstrated massive activation of autophagy in P. lividus embryos, in cadmium stress conditions, and the existence of a temporal relationship between induced autophagy end …
H2O2 INDUCES NECROPTOSIS IN MESOANGIOBLAST STEM CELLS
2018
Stem cells are used in regenerative medicine, but their therapeutic efficacy is compromised by their huge death during the first days post-transplantation. Indeed, the microenvironment within damaged tissues is hostile for stem cell survival mainly due to oxidative stress. H2O2 may play a relevant role in inducing death of the injected cells. The aim of our study was to determine the mechanism of mesoangioblast (A6) cell death after an H2O2 treatment. FACS analysis with annV/PI showed that H2O2 induced a dose and time-dependent decrement in A6 viability. We have also found an increase in caspases 8, 9 and 3 activity after the treatment. To assess their involvement in cell death, the pan cas…
Relazione tra autofagia e apoptosi in embrioni di riccio di mare esposti a stress
2012
L’embrione di riccio di mare Paracentrotus lividus è stato utilizzato come organismo modello della biologia dello sviluppo per molti anni ed è considerato il deuterostoma più primitivo, con scheletro calcificato, correlato a protocordati e vertebrati. Tale sistema offre un'eccellente opportunità per studiare le numerose strategie di difesa che gli embrioni mettono in atto contro diverse condizioni di stress. In precedenza, abbiamo riportato che l’esposizione di embrioni a dosi citotossiche di cadmio, provoca l'accumulo intracellulare del metallo e l'attivazione del sistema difensivo, in modo dose-tempo dipendente, attraverso la sintesi di specifiche HSPs e/o l’innesco di apoptosi. Mediante …