Search results for "mitochondrial"

Mitochondrial sequence analysis of Salamandra taxa suggests old splits of major lineages and postglacial recolonizations of Central Europe from disti…

2000

Representatives of the genus Salamandra occur in Europe, Northern Africa and the Near East. Many local variants are known but species and subspecies status of these is still a matter of dispute. We have analysed samples from locations covering the whole expansion range of Salamandra by sequence analysis of mitochondrial D-loop regions. In addition, we have calibrated the rate of divergence of the D-loop on the basis of geologically dated splits of the closely related genus Euproctus. Phylogenetic analysis of the sequences suggests that six major monophyletic groups exist (S. salamandra, S. algira, S. infraimmaculata, S. corsica, S. atra and S. lanzai) which have split between 5 and 13 milli…

Aplidin® induces JNK-dependent apoptosis in human breast cancer cells via alteration of glutathione homeostasis, Rac1 GTPase activation, and MKP-1 ph…

2006

Aplidin® is an antitumor agent in phase II clinical trials that induces apoptosis through the sustained activation of Jun N-terminal kinase (JNK). We report that Aplidin® alters glutathione homeostasis increasing the ratio of oxidized to reduced forms (GSSG/GSH). Aplidin® generates reactive oxygen species and disrupts the mitochondrial membrane potential. Exogenous GSH inhibits these effects and also JNK activation and cell death. We found two mechanisms by which Aplidin® activates JNK: rapid activation of Rac1 small GTPase and downregulation of MKP-1 phosphatase. Rac1 activation was diminished by GSH and enhanced by L-buthionine (SR)-sulfoximine, which inhibits GSH synthesis. Downregulatio…

Biological and Proteomic Characterization of the Anti-Cancer Potency of Aqueous Extracts from Cell-Free Coelomic Fluid of Arbacia lixula Sea Urchin i…

2022

Echinoderms are an acknowledged source of bioactive compounds exerting various beneficial effects on human health. Here, we examined the potential in vitro anti-hepatocarcinoma effects of aqueous extracts of the cell-free coelomic fluid obtained from the sea urchin Arbacia lixula using the HepG2 cell line as a model system. This was accomplished by employing a combination of colorimetric, microscopic and flow cytometric assays to determine cell viability, cell cycle distribution, the possible onset of apoptosis, the accumulation rate of acidic vesicular organelles, mitochondrial polarization, cell redox state and cell locomotory ability. The obtained data show that exposed HepG2 cells under…

Antioxidant Therapies and Oxidative Stress in Friedreich´s Ataxia: The Right Path or Just a Diversion?

2020

Friedreich's ataxia is the commonest autosomal recessive ataxia among population of European descent. Despite the huge advances performed in the last decades, a cure still remains elusive. One of the most studied hallmarks of the disease is the increased production of oxidative stress markers in patients and models. This feature has been the motivation to develop treatments that aim to counteract such boost of free radicals and to enhance the production of antioxidant defenses. In this work, we present and critically review those 'antioxidant' drugs that went beyond the disease's models and were approved for its application in clinical trials. The evaluation of these trials highlights some …

Silibin hepatoprotection occur via NFKB signaling inhibition in murine nonalcholic fatty liver disease

2009

The oxidative capacity of skeletal muscle : effects of genotype, high-fat diet and physical activity

2016

The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and Cilia to Regulate Ciliogenesis and Ciliary Protein Traffic

2021

ABSTRACTELMODs are a family of three mammalian paralogs that display GTPase activating protein (GAP) activity towards a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogs ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regu…

Randomized Trial : D-Glyceric Acid Activates Mitochondrial Metabolism in 50–60-Year-Old Healthy Humans

2021

Background: Based on earlier studies, natural metabolite D-glyceric acid (DGA) does not seem to play any role in whole-body metabolism. Nevertheless, one ethanol oxidation-related rat study with controversial results raised our interest. According to preparatory studies for the regulatory approval of DGA, some highly conserved mechanism seems to subtly activate the cellular energy metabolism. Therefore, the present 25-days double-blind human study with placebo control was initiated. Purpose: The main target in the present study with 27 healthy 50–60-year-old human volunteers was to find out whether an “acute” 4-days and a longer 21-days exogenous DGA regimen caused moderate activation of th…

Real-world experience with obeticholic acid in patients with primary biliary cholangitis

2021

Background & aims Obeticholic acid (OCA) is the second-line treatment approved for patients with primary biliary cholangitis (PBC) and an inadequate response or intolerance to ursodeoxycholic acid. We aimed to evaluate the effectiveness and safety of OCA under real-world conditions. Methods Patients were recruited into the Italian PBC Registry, a multicentre, observational cohort study that monitors patients with PBC at national level. The primary endpoint was the biochemical response according to Poise criteria; the secondary endpoint was the biochemical response according to normal range criteria, defined as normal levels of bilirubin, alkaline phosphatase (ALP), and alanine aminotransfer…