Search results for " autophagy"

Cannabinoid-associated cell death mechanisms in tumor models (review)

2012

In recent years, cannabinoids (the active components of Cannabis sativa) and their derivatives have received considerable interest due to findings that they can affect the viability and invasiveness of a variety of different cancer cells. Moreover, in addition to their inhibitory effects on tumor growth and migration, angiogenesis and metastasis, the ability of these compounds to induce different pathways of cell death has been highlighted. Here, we review the most recent results generating interest in the field of death mechanisms induced by cannabinoids in cancer cells. In particular, we analyze the pathways triggered by cannabinoids to induce apoptosis or autophagy and investigate the in…

TRAIL Triggers CRAC-Dependent Calcium Influx and Apoptosis through the Recruitment of Autophagy Proteins to Death-Inducing Signaling Complex

2021

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills various cancer cell types, but also leads to the activation of signaling pathways that favor resistance to cell death. Here, we investigated the as yet unknown roles of calcium signaling and autophagy regulatory proteins during TRAIL-induced cell death in leukemia cells. Taking advantage of the Gene Expression Profiling Interactive Analysis (GEPIA) project, we first found that leukemia patients present a unique TRAIL receptor gene expression pattern that may reflect their resistance to TRAIL. The exposure of NB4 acute promyelocytic leukemia cells to TRAIL induces intracellular Ca2+ influx through a calcium rel…

RAB3GAP1 and RAB3GAP2 modulate basal and rapamycin-induced autophagy

2014

Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, and its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive and depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) are important factors for the coordination of cellular vesicle transport systems, and several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs are associated with autophagy. Employing C. elegans and human primary fibroblasts, we show that RAB3GAP1 and RAB3GAP2, which are components of the TBC domain-free RAB3GAP complex, influence protein aggregation and affect autophagy at basal an…

Autophagy induction in sea urchin embryos exposed to gadolinium ions

2014

Sea urchin embryos are highly sensitive to several kinds of stressors, and able to activate different defense strategies. Gadolinium (Gd) is a metal of the lanthanide series of the elements: its chelates are employed as contrast agents for magnetic resonance imaging since the 1980s. Gd complexes are released in the aquatic environment, making Gd an emergent environmental pollutant. In this study we focused on the effects of Gd ions on sea urchin embryos development. The study was conducted looking at three different processes: general development, apoptosis and autophagy. At the whole morphological level, Paracentrotus lividus sea urchin embryos continuously exposed to Gd ions displayed mor…

Gadolinium induces autophagy in sea urchin embryos

2014

Rare ATG7 genetic variants predispose patients to severe fatty liver disease

2022

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of liver disorders and has a strong heritable component. The aim of this study was to identify new loci that contribute to severe NAFLD by examining rare variants.Methods: We performed whole-exome sequencing in in-dividuals with NAFLD and advanced fibrosis or hepatocellular carcinoma (n = 301) and examined the enrichment of likely pathogenic rare variants vs. the general population. This was followed by validation at the gene level.Results: In patients with severe NAFLD, we observed an enrichment of the p.P426L variant (rs143545741 C>T; odds ratio [OR] 5.26, 95% CI 2.1-12.6; p = 0.003) of autophagy-rela…

Guidelines for the use and interpretation of assays for monitoring cell death in higher eukaryotes

2009

Cell death is essential for a plethora of physiological processes, and its deregulation characterizes numerous human diseases. Thus, the in-depth investigation of cell death and its mechanisms constitutes a formidable challenge for fundamental and applied biomedical research, and has tremendous implications for the development of novel therapeutic strategies. It is, therefore, of utmost importance to standardize the experimental procedures that identify dying and dead cells in cell cultures and/or in tissues, from model organisms and/or humans, in healthy and/or pathological scenarios. Thus far, dozens of methods have been proposed to quantify cell death-related parameters. However, no guid…

Long-Term Calorie Restriction Enhances Cellular Quality-Control Processes in Human Skeletal Muscle

2015

Calorie restriction (CR) retards aging, acts as a hormetic intervention, and increases serum corticosterone and HSP70 expression in rodents. However, less is known regarding the effects of CR on these factors in humans. Serum cortisol and molecular chaperones and autophagic proteins were measured in the skeletal muscle of subjects on CR diets for 3-15 years and in control volunteers. Serum cortisol was higher in the CR group than in age-matched sedentary and endurance athlete groups (15.6 ± 4.6 ng/dl versus 12.3 ± 3.9 ng/dl and 11.2 ± 2.7 ng/dl, respectively; p ≤ 0.001). HSP70, Grp78, beclin-1, and LC3 mRNA and/or protein levels were higher in the skeletal muscle of the CR group compared to…

Oxidative stress induced by the novel compound tributyltin(iv) ferulate promotes ER stress and autophagy in colon cancer cells

2021

The HDAC inhibitor SAHA synergistically stimulates the cytotoxic effect induced by Parthenolide in MDA-MB231 cells

2014

We showed that the sesquiterpene lactone Parthenolide (PN) exerts strong cytotoxic effects on triple negative breast cancer MDA-MB231 cells. Our recent results suggest that PN exerts in these cells a cytoprotective effect, which is due to the activation of mTOR pathway. To inhibit this protective response we employ the HDAC inhibitor SAHA, which is known to prevent AKT/mTOR pathway. We show that PN activates Akt, mTOR, p70S6kinase and NRF2 while SAHA abolishes these effects. Further cell pretreatment with SAHA synergistically sensitizes the cells to the cytotoxic effect of PN. Moreover SAHA alone activates the autophagic process. The addition of PN to SAHA reduces this effect and induces ap…