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Sean Ekins et al.
Drug metabolism and disposition: the biological fate of chemicals, 38(12), 2302-2308 (2010-09-17)
Drug-induced liver injury (DILI) is one of the most important reasons for drug development failure at both preapproval and postapproval stages. There has been increased interest in developing predictive in vivo, in vitro, and in silico models to identify compounds
Hamidullah Khan et al.
Cell reports, 29(10), 3009-3018 (2019-12-05)
Metabolic flexibility allows cells to adapt to various environments and limits the efficacy of metabolic drugs. Therapeutic targeting of cancer metabolism relies on defining limiting requirements and vulnerabilities in the highly dynamic metabolic network. Here, we characterize the metabolic reprogramming
Francisco J Rios et al.
The Journal of pharmacology and experimental therapeutics, 353(1), 27-34 (2015-01-27)
Hyperaldosteronism and hypertension were unexpected side effects observed in trials of torcetrapib, a cholesteryl ester-transfer protein (CETP) inhibitor that increases high-density lipoprotein. Given that CETP inhibitors are lipid soluble, accumulate in adipose tissue, and have binding sites for proteins involved
Xiaoling Chen et al.
The British journal of nutrition, 123(5), 499-507 (2019-11-30)
The present study aimed to investigate whether arginine (Arg) promotes porcine type I muscle fibres formation via improving mitochondrial biogenesis. In the in vivo study, a total of sixty Duroc × Landrace × Yorkshire weaning piglets with an average body
Brandon Gaitan et al.
Metabolites, 12(11) (2022-11-25)
Breast cancer is the most diagnosed cancer type in women, with it being the second most deadly cancer in terms of total yearly mortality. Due to the prevalence of this disease, better methods are needed for both detection and treatment.
Identification of Dihydroorotate Dehydrogenase Inhibitors Using the Cell Painting Assay.
Sch??lermann, et al.
Chembiochem, 23, e202200475-e202200475 (2023)
Rhianna Williams et al.
Developmental cell, 54(6), 758-772 (2020-08-01)
The loss of protein homeostasis (proteostasis) is a primary driver of age-related tissue dysfunction. Recent studies have revealed that the failure of proteostasis with age is triggered by developmental and reproductive cues that repress the activity of proteostasis-related pathways in
T Ahmad et al.
Cell death & disease, 4, e461-e461 (2013-01-19)
Dynamic variations in mitochondrial shape have been related to function. However, tools to automatically classify and enumerate mitochondrial shapes are lacking, as are systematic studies exploring the relationship of such shapes to mitochondrial stress. Here we show that during increased
Ximena Corso-Díaz et al.
Cell reports, 31(3), 107525-107525 (2020-04-23)
Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions
Wen-Chih Lee et al.
Cell reports, 32(10), 108108-108108 (2020-09-10)
The metabolic program of osteoblasts, the chief bone-making cells, remains incompletely understood. Here in murine calvarial cells, we establish that osteoblast differentiation under aerobic conditions is coupled with a marked increase in glucose consumption and lactate production but reduced oxygen
Simone Z Vogel et al.
Journal of immunology (Baltimore, Md. : 1950), 194(7), 3136-3146 (2015-03-10)
We previously showed that the T cell activation inhibitor, mitochondrial (Tcaim) is highly expressed in grafts of tolerance-developing transplant recipients and that the encoded protein is localized within mitochondria. In this study, we show that CD11c(+) dendritic cells (DCs), as
Yi-Sheng Hou et al.
Molecular and cellular biology, 35(16), 2740-2751 (2015-06-03)
Dysfunction of the autophagy-lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS) was thought to be an important pathogenic mechanism in synuclein pathology and Parkinson's disease (PD). In the present study, we investigated the role of sestrin2 in autophagic degradation of
Restoration of lysosomal acidification rescues autophagy and metabolic dysfunction in non-alcoholic fatty liver disease.
Zeng, et al.
Nature Communications, 14, 2573-2573 (2023)
Lu Yang et al.
Biochemical and biophysical research communications, 529(2), 296-302 (2020-07-25)
Dedicator of cytokinesis 2 (DOCK2) is essential for the B cell differentiation, BCR signaling and humoral immune response. However, the role of DOCK2 in the memory response of B cell is unknown. By using two DOCK2 deficient patients, we found
Mengxia Li et al.
Free radical biology & medicine, 76, 278-285 (2014-09-17)
DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ataxia telangiectasia mutated (ATM) are the two major kinases involved in DNA double-strand break (DSB) repair, and are required for cellular resistance to ionizing radiation. Whereas ATM is the key upstream kinase for
Yunwen Yang et al.
International urology and nephrology, 51(7), 1207-1218 (2019-04-26)
The dysfunction of mitochondrial respiratory chain induced by cisplatin results in overproduction of reactive oxygen species (ROS) which contributes to kidney injury. The current study aimed to evaluate the effect of a mitochondrial electron transport inhibitors of rotenone (mitochondrial complex
Yuriy Saenko et al.
Radiation research, 180(4), 360-366 (2013-09-17)
Free radicals generated by mitochondria are candidates for mediating long-lasting effects of radiation on cells, including genetic instability. To better understand the significance of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in these long-term effects we assayed ROS
Neal J Dawson et al.
eLife, 9 (2020-07-31)
High-altitude environments require that animals meet the metabolic O2 demands for locomotion and thermogenesis in O2-thin air, but the degree to which convergent metabolic changes have arisen across independent high-altitude lineages or the speed at which such changes arise is
Rawand Masoud et al.
Cell reports. Medicine, 1(8), 100143-100143 (2020-12-10)
Mitochondrial respiration (oxidative phosphorylation, OXPHOS) is an emerging target in currently refractory cancers such as pancreatic ductal adenocarcinoma (PDAC). However, the variability of energetic metabolic adaptations between PDAC patients has not been assessed in functional investigations. In this work, we
Pan Cheng et al.
Cell research, 31(7), 758-772 (2021-01-21)
Ca2+ channels are essential to cell birth, life, and death. They can be externally activated by optogenetic tools, but this requires robust introduction of exogenous optogenetic genes for expression of photosensitive proteins in biological systems. Here we present femtoSOC, a
Suzanna J Logan et al.
Basic research in cardiology, 110(2), 19-19 (2015-03-03)
Ischemic heart disease (IHD) is a leading cause of death worldwide, and regenerative therapies through exogenous stem cell delivery hold promising potential. One limitation of such therapies is the vulnerability of stem cells to the oxidative environment associated with IHD.
Mei Yang et al.
Toxicology and applied pharmacology, 280(1), 117-126 (2014-08-12)
Understanding the molecular mechanisms responsible for the cytotoxic effects of carbon nanomaterials is important for their future biomedical applications. Carbon nanotubular materials induce the generation of reactive oxygen species (ROS), which causes cell death; however, the exact details of this
Alessandro Luciani et al.
Nature communications, 11(1), 970-970 (2020-02-23)
Deregulation of mitochondrial network in terminally differentiated cells contributes to a broad spectrum of disorders. Methylmalonic acidemia (MMA) is one of the most common inherited metabolic disorders, due to deficiency of the mitochondrial methylmalonyl-coenzyme A mutase (MMUT). How MMUT deficiency
Dong Sun Oh et al.
Autophagy, 17(9), 2111-2127 (2020-08-21)
Respiratory syncytial virus (RSV) is a leading cause of respiratory tract infections in infants. Macroautophagy/autophagy is a catalytic metabolic process required for cellular homeostasis. Although intracellular metabolism is important for immune responses in dendritic cells, the link between autophagy and
Justyna McIntyre et al.
The Journal of biological chemistry, 290(45), 27332-27344 (2015-09-16)
Human DNA polymerases (pols) η and ι are Y-family DNA polymerase paralogs that facilitate translesion synthesis past damaged DNA. Both polη and polι can be monoubiquitinated in vivo. Polη has been shown to be ubiquitinated at one primary site. When
Sally Yu Shi et al.
Nature communications, 6, 7415-7415 (2015-06-17)
Reactive oxygen species (ROS) have been linked to a wide variety of pathologies, including obesity and diabetes, but ROS also act as endogenous signalling molecules, regulating numerous biological processes. DJ-1 is one of the most evolutionarily conserved proteins across species
Sijia Yin et al.
Molecular neurobiology, 59(2), 1333-1344 (2022-01-06)
Parkinson's disease (PD) is an incurable neurodegenerative disease characterized by aggregation of pathological alpha-synuclein (α-syn) and loss of dopaminergic neuron in the substantia nigra. Inhibition of phosphorylation of the α-syn has been shown to mediate alleviation of PD-related pathology. Protein
Paramita Chakraborty et al.
Cell reports, 28(7), 1879-1893 (2019-08-15)
Sphingosine 1-phosphate (S1P), a bioactive lysophospholipid generated by sphingosine kinase 1 (SphK1), regulates lymphocyte egress into circulation via S1P receptor 1 (S1PR1) signaling, and it controls the differentiation of regulatory T cells (Tregs) and T helper-17 cells. However, the mechanisms by
S Schüll et al.
Cell death & disease, 6, e1691-e1691 (2015-03-15)
Although numerous pathogenic changes within the mitochondrial respiratory chain (RC) have been associated with an elevated occurrence of apoptosis within the affected tissues, the mechanistic insight into how mitochondrial dysfunction initiates apoptotic cell death is still unknown. In this study
Nicole Baker et al.
Cell stem cell, 29(9), 1315-1332 (2022-08-24)
Quiescence regulation is essential for adult stem cell maintenance and sustained regeneration. Our studies uncovered that physiological changes in mitochondrial shape regulate the quiescent state of adult muscle stem cells (MuSCs). We show that MuSC mitochondria rapidly fragment upon an
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