Search results for " ER stress"

Current disease modifying approaches to treat Parkinson's disease

2015

Parkinson's disease (PD is a progressive neurological disorder characterized by the degeneration and death of midbrain dopamine and non-dopamine neurons in the brain leading to motor dysfunctions and other symptoms, which seriously influence the quality of life of PD patients. The drug L-dopa can alleviate the motor symptoms in PD, but so far there are no rational therapies targeting the underlying neurodegenerative processes. Despite intensive research, the molecular mechanisms causing neuronal loss are not fully understood which has hampered the development of new drugs and disease-modifying therapies. Neurotrophic factors are by virtue of their survival promoting activities attract candi…

WIN induces apoptotic cell death in human colon cancer cells through a block of autophagic flux dependent on PPARγ down-regulation.

2014

Cannabinoids have been reported to possess anti-tumorigenic activity in cancer models although their mechanism of action is not well understood. Here, we show that the synthetic cannabinoid WIN55,212-2 (WIN)-induced apoptosis in colon cancer cell lines is accompanied by endoplasmic reticulum stress induction. The formation of acidic vacuoles and the increase in LC3-II protein indicated the involvement of autophagic process which seemed to play a pro-survival role against the cytotoxic effects of the drug. However, the enhanced lysosomal membrane permeabilization (LMP) blocked the autophagic flux after the formation of autophagosomes as demonstrated by the accumulation of p62 and LC3, two ma…

Hypertrophy and ER Stress Induced by Palmitate Are Counteracted by Mango Peel and Seed Extracts in 3T3-L1 Adipocytes

2023

A diet rich in saturated fatty acids (FAs) has been correlated with metabolic dysfunction and ROS increase in the adipose tissue of obese subjects. Thus, reducing hypertrophy and oxidative stress in adipose tissue can represent a strategy to counteract obesity and obesity-related diseases. In this context, the present study showed how the peel and seed extracts of mango (Mangifera indica L.) reduced lipotoxicity induced by high doses of sodium palmitate (PA) in differentiated 3T3-L1 adipocytes. Mango peel (MPE) and mango seed (MSE) extracts significantly lowered PA-induced fat accumulation by reducing lipid droplet (LDs) and triacylglycerol (TAGs) content in adipocytes. We showed that MPE a…

The new murine hepatic 3A cell line responds to stress stimuli by activating an efficient Unfolded Protein Response (UPR)

2012

In the present study we have investigated the properties of a novel cell line (3A cells) obtained from the liver of 14.5. days post coitum (dpc) wild-type mouse embryo. 3A cells morphology was characterized by fluorescent localization of F-actin and β-catenin. The expression of specific genes and proteins essential to liver function in these cells was comparable or even more efficient then in the differentiated hepatocytic cell line MMH-D6. 3A cells also showed the capability to excrete molecules in extracellular spaces resembling functional bile canaliculi, glycogen storage activity and the ability to control retinol-binding protein 4 secretion in response to retinol deprivation. Their re…

UNRAVELLING THE ROLES OF THE NUCLEAR PROTEIN 1 DURING ER-STRESS INDUCTION

2020

Background: NUPR1 was described as a transcriptional factor involved in the regulation of various cellular stress-response genes, playing a crucial role in the condition of the endoplasmic-reticulum (ER) stress, thus emerging as a common molecular factor of different pathologies, obesity, hepatic steatosis, and cancer. In the present work we aim to explore how NUPR1 interacts with some pivotal genes that are the major modulators of the ER stress and metabolic cell functions. In particular we investigated the biochemical and molecular effects arising from the loss of NUPR1 in ER stress physiological conditions. Methods: We used prolonged high fat diet (HFD) feeding to induce ER stress physio…

Involvement of PAR-4 in Cannabinoid-Dependent Sensitization of Osteosarcoma Cells to TRAIL-Induced Apoptosis

2014

The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential. Experiments were performed to determine the effects of WIN on proliferation, cell cycle distribution, and programmed cell death in human osteosarcoma MG63 and Saos-2 cells. Results show that WIN induced G2/M cell cycle arrest, which was associated with the induction of the main markers of ER stress (GRP78, CHOP and TRB3). In treated cells we also observed the conversion of the cytosolic form of the autophagosome marker LC3-I into LC3-II (the lipidated form located on the autophagosome membrane) and the enhanced incorporation of monodansylcadaverine and acridine orange, two markers of t…

Effects of 5-Azacitidine on Dnmt2/Trdmt1 expression levels and endoplasmic reticulum stress in cellular models of insulinoma

2021

Diabetes mellitus affects people all over the world of all ages or social groups making it a worldwide healthcare challenge. Moreover, untreated or badly treated diabetes carries a risk of serious complications including premature death (IDF Diabetes Atlas 9th edition, 2019). The main symptom of diabetes is insulin secretion and/or action disorder leading to hyperglycemia what results in impaired carbohydrate, fat, and protein metabolism (“Diagnosis and Classification of Diabetes Mellitus,” 2013). Dnmt2/ Trdmt1 in its structure and sequence is similar to DNA methyltransferases, however, it has been shown that mainly methylates aspartic acid transfer RNA, specifically at the cytosine-38 resi…

Studio dei meccanismi molecolari di risposta al sorafenib e identificazione di nuovi bersagli terapeutici per il trattamento del carcinoma epatocellu…

Targeting the Endoplasmic Reticulum Unfolded Protein Response to Counteract the Oxidative Stress-Induced Endothelial Dysfunction

2017

In endothelial cells, the tight control of the redox environment is essential for the maintenance of vascular homeostasis. The imbalance between ROS production and antioxidant response can induce endothelial dysfunction, the initial event of many cardiovascular diseases. Recent studies have revealed that the endoplasmic reticulum could be a new player in the promotion of the pro- or antioxidative pathways and that in such a modulation, the unfolded protein response (UPR) pathways play an essential role. The UPR consists of a set of conserved signalling pathways evolved to restore the proteostasis during protein misfolding within the endoplasmic reticulum. Although the first outcome of the U…