Search results for "Pyruvate"

Structural Manipulations of Marine Natural Products Inspire a New Library of 3-Amino-1,2,4-Triazine PDK Inhibitors Endowed with Antitumor Activity in…

2023

Pancreatic ductal adenocarcinoma (PDAC) is one of the main aggressive types of cancer, characterized by late prognosis and drug resistance. Among the main factors sustaining PDAC progression, the alteration of cell metabolism has emerged to have a key role in PDAC cell proliferation, invasion, and resistance to standard chemotherapeutic agents. Taking into account all these factors and the urgency in evaluating novel options to treat PDAC, in the present work we reported the synthesis of a new series of indolyl-7-azaindolyl triazine compounds inspired by marine bis-indolyl alkaloids. We first assessed the ability of the new triazine compounds to inhibit the enzymatic activity of pyruvate de…

Aging of the liver: Age-associated mitochondrial damage in intact hepatocytes

1996

Mitochondrial damage may be a major cause of cellular aging. So far, this hypothesis had only been tested using isolated mitochondria. The aim of this study was to investigate the involvement of mitochondria in aging using whole liver cells and not isolated mitochondria only. Using flow cytometry, we found that age is associated with a decrease in mitochondrial membrane potential (30%), an increase in mitochondrial size, and an increase in mitochondrial peroxide generation (23%). Intracellular peroxide levels were also increased. The number of mitochondria per cell and inner mitochondrial membrane mass did not change. Gluconeogenesis from glycerol or fructose (mitochondrial-independent) did…

c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis.

2001

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. e…

2019

Mitochondria have been increasingly recognized as a central regulatory nexus for multiple metabolic pathways, in addition to ATP production via oxidative phosphorylation (OXPHOS). Here we show that inducing mitochondrial DNA (mtDNA) stress in Drosophila using a mitochondrially-targeted Type I restriction endonuclease (mtEcoBI) results in unexpected metabolic reprogramming in adult flies, distinct from effects on OXPHOS. Carbohydrate utilization was repressed, with catabolism shifted towards lipid oxidation, accompanied by elevated serine synthesis. Cleavage and translocation, the two modes of mtEcoBI action, repressed carbohydrate rmetabolism via two different mechanisms. DNA cleavage activ…