The P2X4 purinergic receptor regulates hepatic myofibroblast activation during liver fibrogenesis.

Background & Aims: Liver fibrosis is characterized by the accumulation of extracellular matrix produced by hepatic myofibroblasts (hMF), the activation of which is critical to the fibrogenic process. Extracellular ATP, released by dying or stressed cells, and its purinergic receptors, constitute a powerful signaling network after injury. Although the purinergic receptor P2X4 (P2RX4) is highly expressed in the liver, its functions in hMF had never been investigated during liver fibrogenesis.

The P2X4 purinergic receptor impacts liver regeneration after partial hepatectomy in mice through the regulation of biliary homeostasis.

Unlabelled: Many regulatory pathways are involved in liver regeneration after partial hepatectomy (PH), to initiate growth, protect liver cells, and sustain remnant liver functions. Extracellular adenosine triphosphate rises in blood and bile after PH and contributes to liver regeneration, although purinergic receptors and mechanisms remain to be precisely explored. In this work we analyzed during regeneration after PH the involvement of P2X4 purinergic receptors, highly expressed in the liver.

Deficiency of multidrug resistance 2 contributes to cell transformation through oxidative stress.

Multidrug resistance 2 (Mdr2), also called adenosine triphosphate-binding cassette B4 (ABCB4), is the transporter of phosphatidylcholine (PC) at the canalicular membrane of mouse hepatocytes, which plays an essential role for bile formation. Mutations in human homologue MDR3 are associated with several liver diseases. Knockout of Mdr2 results in hepatic inflammation, liver fibrosis and hepatocellular carcinoma (HCC).

Caspase-dependent Proteolysis of Human Ribonucleotide Reductase Small Subunits R2 and p53R2 during Apoptosis.

Ribonucleotide reductase (RnR) is a key enzyme synthesizing deoxyribonucleotides for DNA replication and repair. In mammals, the R1 catalytic subunit forms an active complex with either one of the two small subunits R2 and p53R2. Expression of R2 is S phase-specific and required for DNA replication.

LIM-only protein FHL2 activates NF-κB signaling in the control of liver regeneration and hepatocarcinogenesis.

Four-and-a-half LIM-only protein 2 (FHL2) is an important mediator in many signaling pathways. In this study, we analyzed the functions of FHL2 in nuclear factor κB (NF-κB) signaling in the liver. We show that FHL2 enhanced tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) activity in transcriptional activation of NF-κB targets by stabilizing the protein.

Early mitochondrial adaptations in skeletal muscle to diet-induced obesity are strain dependent and determine oxidative stress and energy expenditure but not insulin sensitivity.

This study sought to elucidate the relationship between skeletal muscle mitochondrial dysfunction, oxidative stress, and insulin resistance in two mouse models with differential susceptibility to diet-induced obesity. We examined the time course of mitochondrial dysfunction and insulin resistance in obesity-prone C57B and obesity-resistant FVB mouse strains in response to high-fat feeding. After 5 wk, impaired insulin-mediated glucose uptake in skeletal muscle developed in both strains in the absence of any impairment in proximal insulin signaling.

TAp73 induction by nitric oxide: regulation by checkpoint kinase 1 (CHK1) and protection against apoptosis.

Nitric oxide (NO) is a potent activator of the p53 tumor suppressor protein, thereby inducing cell cycle arrest and apoptosis. However, little is known about the regulation of the two other p53-family members, p63 and p73, by nitrogen oxides. We report here an up-regulation of p73 by NO in p53-null K-562 leukemia cells.

Anti-tumoral effect of a celecoxib low dose on a model of human medullary thyroid cancer in nude mice.

Background: Medullary thyroid carcinoma (MTC) is a C cell neoplasm secreting calcitonin (CT). Surgery remains the only treatment as MTC is resistant to radio- and chemotherapies. Anti-tumoral effects of nonsteroidal anti-inflammatory drugs have been observed in various cancers.

Upregulation of the p53R2 ribonucleotide reductase subunit by nitric oxide.

The p53R2 ribonucleotide reductase subunit is a p53-inducible protein involved in DNA repair and mitochondrial DNA replication. It has been shown that p53 is activated by nitric oxide, which can damage DNA at high concentrations. This suggests that NO may regulate p53R2 expression through p53 activation.