Search results for "ATP"

Reversal of multidrug resistance by Marsdenia tenacissima and its main active ingredients polyoxypregnanes.

2016

Abstract Ethnopharmacological relevance Multidrug resistance (MDR) of cancer is often associated with the overexpression of ATP-binding cassette (ABC) transporters, such as P-glycoprotein (P-gp), multidrug resistance-associated protein-1 (MRP-1) and breast cancer resistance protein (BCRP or ABCG2), in cancer cells, which facilitates the active efflux of a wide variety of chemotherapeutic drugs out of the cells. Marsdenia tenacissima is a traditional Chinese medicinal herb that has long been clinically used for treatment of cancers, particularly in combinational use with anticancer drugs. Polyoxypregnanes (POPs) are identified as main constituents of this herb, and three of them have been re…

Topical Review: The Neuronal Ceroid-Lipofuscinoses

1995

The neuronal ceroid-lipofuscinoses, a group of progressive neurodegenerative diseases in children and in adults, have now been recognized for some 90 years, and the childhood forms represent one of the largest groups of progressive neurodegenerative diseases in children. Apart from a core group of major clinical forms—the infantile, the late-infantile, the juvenile, and the adult forms—numerous atypical patients afflicted with neuronal ceroid-lipofuscinosis have now been identified, constituting 10% to 20% of all patients with neuronal ceroid-lipofuscinosis. These "atypical" patients have, over the past 10 years, prompted the suggestion of 15 atypical variants or minor syndromes, many of th…

miR-22 suppresses DNA ligase III addiction in multiple myeloma

2019

Multiple myeloma (MM) is a hematologic malignancy characterized by high genomic instability. Here we provide evidence that hyper-activation of DNA ligase III (LIG3) is crucial for genomic instability and survival of MM cells. LIG3 mRNA expression in MM patients correlates with shorter survival and even increases with more advanced stage of disease. Knockdown of LIG3 impairs MM cells viability in vitro and in vivo, suggesting that neoplastic plasmacells are dependent on LIG3-driven repair. To investigate the mechanisms involved in LIG3 expression, we investigated the post-transcriptional regulation. We identified miR-22-3p as effective negative regulator of LIG3 in MM. Enforced expression of…

Effects of ibuprofen and carbamazepine on the ion transport system and fatty acid metabolism of temperature conditioned juveniles of Solea senegalens…

2018

The increasing presence of pharmaceuticals in aquatic environments in the last decades, derived from human and veterinary use, has become an important environmental problem. Previous studies have shown that ibuprofen (IB) and carbamazepine (CBZ) modify physiological and biochemical processes in Senegalese sole (Solea senegalensis) in a temperature-dependent manner. In other vertebrates, there is evidence that both of these pharmaceuticals interfere with the ‘arachidonic acid (AA) cascade’, which is responsible for the biosynthesis of numerous enzymes that are involved in the osmoregulatory process. The present work aims to study the temperature-dependent effects of these two pharmaceuticals…

Where do we go from here? Membrane protein research beyond the structure-function horizon.

2018

PI3K inhibition reduces murine and human liver fibrogenesis in precisioncut liver slices

2019

Background: Liver fibrosis results from continuous inflammation and injury. Despite its high prevalence worldwide, no approved antifibrotic therapies exist. Omipalisib is a selective inhibitor of the PI3K/mTOR pathway that controls nutrient metabolism, growth and proliferation. It has shown antifibrotic properties in vitro. While clinical trials for idiopathic pulmonary fibrosis have been initiated, an in-depth preclinical evaluation is lacking. We evaluated omipalisib's effects on fibrogenesis using the ex vivo model of murine and human precision-cut tissue slices (PCTS).Methods: Murine and human liver and jejunum PCTS were incubated with omipalisib up to 10 mu M for 48 h. PI3K pathway act…

Biallelic variants in LARS2 and KARS cause deafness and (ovario)leukodystrophy

2019

Supplemental Digital Content is available in the text.

Skeletal muscle-specific methyltransferase METTL21C trimethylates p97 and regulates autophagy-associated protein breakdown

2018

Summary: Protein aggregates and cytoplasmic vacuolization are major hallmarks of multisystem proteinopathies (MSPs) that lead to muscle weakness. Here, we identify METTL21C as a skeletal muscle-specific lysine methyltransferase. Insertion of a β-galactosidase cassette into the Mettl21c mouse locus revealed that METTL21C is specifically expressed in MYH7-positive skeletal muscle fibers. Ablation of the Mettl21c gene reduced endurance capacity and led to age-dependent accumulation of autophagic vacuoles in skeletal muscle. Denervation-induced muscle atrophy highlighted further impairments of autophagy-related proteins, including LC3, p62, and cathepsins, in Mettl21c−/− muscles. In addition, w…

The concerted amyloid-beta clearance of LRP1 and ABCB1/P-gp across the blood-brain barrier is linked by PICALM

2018

The accumulation of neurotoxic amyloid-beta (Aβ) in the brain is a characteristic hallmark of Alzheimer's disease (AD). The blood-brain barrier (BBB) provides a large surface area and has been shown to be an important mediator for removal of brain Aβ. Both, the ABC transporter P-glycoprotein (ABCB1/P-gp) and the receptor low-density lipoprotein receptor-related protein 1 (LRP1) have been implicated to play crucial roles in Aβ efflux from brain. Here, with immunoprecipitation experiments, co-immunostainings and dual inhibition of ABCB1/P-gp and LRP1, we show that both proteins are functionally linked, mediating a concerted transcytosis of Aβ through endothelial cells. Late-onset AD risk fact…

LXR agonist treatment of blastic plasmacytoid dendritic cell neoplasm restores cholesterol efflux and triggers apoptosis

2016

International audience; Blastic plasmacytoid dendritic cell (PDC) neoplasm (BPDCN) is an aggressive hematological malignancy with a poor prognosis that derives from PDCs. No consensus for optimal treatment modalities is available today and the full characterization of this leukemia is still emerging. We identified here a BPDCN-specific transcriptomic profile when compared with those of acute myeloid leukemia and T-acute lymphoblastic leukemia, as well as the transcriptomic signature of primary PDCs. This BPDCN gene signature identified a dysregulation of genes involved in cholesterol homeostasis, some of them being liver X receptor (LXR) target genes. LXR agonist treatment of primary BPDCN …