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Showing papers in "Journal of Biological Chemistry in 2013"


Journal ArticleDOI
TL;DR: Two small molecule RIP3 kinase inhibitors are described and employ them to demonstrate the common requirement for RIP3 Kinase in programmed necrosis induced by RIP1-RIP3, DAI- RIP3, and TRIF-RIP 3 complexes.

715 citations


Journal ArticleDOI
TL;DR: Peroxynitrite is the product of the diffusion-controlled reaction of nitric oxide and superoxide radicals, which affects mitochondrial function and triggers cell death via oxidation and nitration reactions.

643 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the neutral sphyngomyelinase 2 (nSMase2) regulates exosomal microRNA (miRNA) secretion and promotes angiogenesis within the tumor microenvironment as well as metastasis, suggesting that the horizontal transfer of exosome miRNAs from cancer cells can dictate the microenviromental niche for the benefit of the cancer cell.

617 citations


Journal ArticleDOI
TL;DR: The lipid raft-associated protein caveolin-1 (CAV1), in analogy with its previously described role in virus uptake, negatively regulates the uptake of exosomes and induces the phosphorylation of several downstream targets known to associate with lipid rafts as signaling and sorting platforms, such as extracellular signal-regulated kinase-1/2 and heat shock protein 27 (HSP27).

553 citations


Journal ArticleDOI
TL;DR: The catalytic ability of all sirtuins to hydrolyze 13 different acyl groups from histone H3 peptides, ranging in carbon length, saturation, and chemical diversity, is investigated, finding that long-chain deacylation is a general feature of mammalian sIRTuins, that SIRT1 and SIRT2 act as efficient decrotonylases, and that SIRs can remove lipoic acid.

518 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the administration of a probiotic, VSL#3, prevented and treated obesity and diabetes in several mouse models and suggested that probiotics can modulate the gut microbiota-SCFA-hormone axis.

516 citations



Journal ArticleDOI
TL;DR: Remarkably, misfolded Tau can be internalized at the somatodendritic compartment, or the axon terminals and it can be transported anterogradely, retrogradely, and can enhance tauopathy in vivo.

446 citations


Journal ArticleDOI
TL;DR: Natural blends of phytochemicals present in the root exudates can modulate the soil microbiome in the absence of the plant, implying that phenolic compounds act as specific substrates or signaling molecules for a large group of microbial species in the soil.

420 citations


Journal ArticleDOI
TL;DR: It is demonstrated that the physiologic pH and acyl-CoA concentrations of the mitochondrial matrix are sufficient to cause dose- and time-dependent, but enzyme-independent acetylation and succinylation of mitochondrial and nonmitochondrial proteins in vitro.

402 citations


Journal ArticleDOI
TL;DR: It is demonstrated that hypoxia-inducible factor 1 (HIF-1) is a critical regulator of ECM remodeling by fibroblasts under hypoxic conditions, which induces changes in breast cancer cell morphology, adhesion, and motility that promote invasion and metastasis.

Journal ArticleDOI
TL;DR: Intracellular TEM interactome is characterized by high throughput mass spectrometry, in both human lymphoblasts and their derived exosomes, revealing a clear pattern of interaction networks and providing evidence that insertion into TEM may be necessary for protein inclusion into the exosome structure.

Journal ArticleDOI
TL;DR: The results suggest that Parkin plays a critical role in adapting to stress in the myocardium by promoting removal of damaged mitochondria in response to myocardial infarction.

Journal ArticleDOI
TL;DR: A novel role for ascorbate is uncovered in modulating the epigenetic control of genome activity by acting as a co-factor for Tet methylcytosine dioxygenase to hydroxylate 5-mC in DNA.

Journal ArticleDOI
TL;DR: It is demonstrated that enhancing Bnip3-Atg8 interactions via phosphorylation-mimicked LIR mutations increased mitochondrial sequestration, lysosomal delivery, and degradation, and Importantly, mitochondria were targeted by mitophagy prior to cytochrome c release, resulting in reduced cellular cytochrom c release capacity.

Journal ArticleDOI
TL;DR: Maintenance of the cellular redox balance is crucial for cell survival and has the potential to mediate extensive yet fully reversible structural and functional changes, rapidly adjusting the protein's activity to the prevailing oxidant levels.

Journal ArticleDOI
TL;DR: A new neuron-to-astrocyte communication pathway is characterized and miRNAs that modulate GLT1 protein expression in astrocytes in vitro and in vivo are identified.

Journal ArticleDOI
TL;DR: It is demonstrated that these metabolic pressures are experienced by Mtb inside its host macrophage and that the bacterium accesses host fatty acid stores and alleviates the pressure from propionyl-CoA.

Journal ArticleDOI
TL;DR: It is demonstrated that cancer cells and their exosomes have altered miRNA profiles under hypoxic conditions, including miR-210, which affected the behavior of endothelial cells.

Journal ArticleDOI
TL;DR: Among 10 TMEM16 family members, 7 members could be divided into two subfamilies, Ca2+-dependent Cl− channels (16A and 16B) and Ca2-dependent lipid scramblases (16C, 16D, 16F, 16G, and 16J).

Journal ArticleDOI
TL;DR: Data strongly suggest that a caveolin-chaperone complex is a mechanism by which newly synthesized cholesterol is transported from the endoplasmic reticulum through the cytoplasm to caveolae.

Journal ArticleDOI
TL;DR: Evaluating HDAC inhibitor properties using histone acetylation is not predictive of their function on cellular activity, and a panel of benzamide-containingHDACi are slow tight-binding inhibitors with long residence times unlike the hydroxamate-containing HDACi vorinostat and trichostatin-A.

Journal ArticleDOI
TL;DR: Kinetic parameters of inhibition as well as acyl enzyme stability are reported against six clinically relevant enzymes, providing the foundation for future structural and mechanistic enzymology experiments.

Journal ArticleDOI
TL;DR: Some of the known regulatory mechanisms affecting enzymes beyond HMGCR are introduced and the need to further investigate their control is highlighted.

Journal ArticleDOI
TL;DR: A number of permutations on the P450 theme reveal the diversity of cytochrome P450 form and function.

Journal ArticleDOI
TL;DR: It is reported that mitochondrial reactive oxygen species (ROS) generated at complex III are required for TGF-β-induced gene expression in primary normal human lung fibroblasts and that targeting mitochondrial ROS might be beneficial in diseases associated with excessive fibrosis.

Journal ArticleDOI
TL;DR: These studies reveal that heparanase helps drive exosome secretion, altersExosome composition, and facilitates production of exosomes that impact both tumor and host cell behavior, thereby promoting tumor progression.

Journal ArticleDOI
TL;DR: The results suggest that levels of lamin A have a marked effect on the ability of neutrophils to passage through micron-scale constrictions, whereas the unusual multilobed shape of the neutrophil nucleus is less essential.

Journal ArticleDOI
TL;DR: The data suggest that acidic environment represents a novel endogenous danger signal alerting the innate immunity, and may contribute to inflammation in acidosis-associated pathologies such as atherosclerosis and post-ischemic inflammatory responses.

Journal ArticleDOI
TL;DR: S-glutathionylated serum proteins may be useful as biomarkers in individuals exposed to agents that cause oxidative or nitrosative stress and also regulate certain protein functional clusters, including those involved in redox-dependent cell signaling events.