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Showing papers in "Journal of Biological Chemistry in 2012"


Journal ArticleDOI
TL;DR: This paper showed that exosome-associated tau secreted by M1C cells occurs via exosomal release, a widely characterized mechanism that mediates unconventional secretion of other aggregation-prone proteins (α-synuclein, prion protein, and β-amyloid) in neurodegenerative disease.

823 citations


Journal ArticleDOI
TL;DR: The GABAA receptors are the major inhibitory neurotransmitter receptors in mammalian brain and respond to a wide variety of drugs, e.g. benzodiazepines, which are often used for their sedative/hypnotic and anxiolytic effects.

611 citations


Journal ArticleDOI
TL;DR: In mouse macrophages, signaling by the pattern recognition receptor TLR4 through MyD88 can rapidly and non-transcriptionally prime NLRP3 by stimulating its deubiquitination, which could explain how NL RP3 is activated by diverse danger signals.

598 citations


Journal ArticleDOI
TL;DR: The data indicate that Bnip3 regulates the apoptotic balance as an autophagy receptor that induces removal of both mitochondria and ER and that this process significantly reduced both mitophagy and ERphagy.

566 citations


Journal ArticleDOI
TL;DR: It is found that when complex I and complex III are inhibited and succinate concentration is low, complex II in rat skeletal muscle mitochondria can generate superoxide or H2O2 at high rates, which approach or exceed the maximum rates achieved by complex I or complex III.

545 citations


Journal ArticleDOI
TL;DR: It is observed that intracellular Tau fibrils are directly released into the medium and then taken up by co-cultured cells, which supports the model of aggregate propagation by templated conformational change and suggest a mechanism for vaccine-based therapies in neurodegenerative diseases.

510 citations


Journal ArticleDOI
TL;DR: It is shown that fructose also stimulates triglyceride synthesis via a purine-degrading pathway that is triggered from the rapid phosphorylation of fructose by fructokinase, which provides new insights into the pathogenesis of hepatic fat accumulation under normal and diseased states.

503 citations


Journal ArticleDOI
TL;DR: Wang et al. as discussed by the authors investigated the oligomeric state of α-syn in mouse, rat, and human brains and showed that both human and rodent αsyn expressed in the central nervous system exist predominantly as an unfolded monomer.

493 citations


Journal ArticleDOI
TL;DR: These findings indicate a novel mechanism responsible for clearance of Aβ through its association with exosomes and suggest the modulation of the vesicle release and/or elimination may alter the risk of AD.

484 citations


Journal ArticleDOI
TL;DR: In this paper, a system-based approach was employed to determine the lipidome of brain tissues affected by Alzheimer disease using liquid chromatography-mass spectrometry to profile extracts from the prefrontal cortex, entorhinal cortex, and cerebellum of late-onset AD patients.

478 citations


Journal ArticleDOI
TL;DR: Peroxiredoxins contain an active site cysteine that is sensitive to oxidation by H2O2, and Regulation of Prx via phosphorylation in response to extracellular signals allows the local accumulation of H2 O2 and thereby enables its messenger function.

Journal ArticleDOI
TL;DR: These data provide the first evidence of Nrf2 in control of Bcl-2 expression and apoptotic cell death with implications in antioxidant protection, survival of cancer cells, and drug resistance.

Journal ArticleDOI
TL;DR: Time course analyses suggest than a SQUAMOSA promoter-binding protein domain transcription factor, whose mRNA increases precede that of lipid biosynthesis genes like DGAT1, is a candidate regulator of the nitrogen deficiency responses.

Journal ArticleDOI
TL;DR: It is demonstrated that exosomes derived from resistant anticancer drug-treated HepG2 cells conferred superior immunogenicity in inducing HSP-specific NK cell responses, which provided a clue for finding an efficient vaccine for hepatocellular carcinoma immunotherapy.

Journal ArticleDOI
TL;DR: This work provides direct biochemical and biological evidence establishing an exquisite regulatory relationship between IDH2 and SIRT3 under acute and chronic caloric restriction, and implicates Sirt3 as a potential regulator of IDH 2-dependent functions in cancer cell metabolism.

Journal ArticleDOI
TL;DR: It is revealed that a single patient-derived autoimmune CD8+ T cell clone of pathogenic relevance in human type I diabetes recognizes >one million distinct decamer peptides in the context of a single MHC class I molecule.

Journal ArticleDOI
TL;DR: It is suggested that the increase of TNFα-producing Kupffer cells in the liver is crucial for the early phase of NASH development by promoting blood monocyte infiltration through the production of IP-10 and MCP-1.

Journal ArticleDOI
TL;DR: Several notable examples are reviewed, including the cellular response to hypoxia, aspects of innate immunity, the regulation of autophagy, and stem cell self-renewal capacity, where evidence suggests an important regulatory role for mitochondrial oxidants.

Journal ArticleDOI
TL;DR: Triacylglycerols from plants, familiar to most people as vegetable oils, supply 25% of dietary calories to the developed world and are increasingly a source for renewable biomaterials and fuels.

Journal ArticleDOI
TL;DR: This work has identified alterations in the expression of proteins involved in the movement of Ca2+ across the plasma membrane and subcellular organelles that are potential therapeutic targets for specific cancer subtypes or correlate with prognosis.

Journal ArticleDOI
TL;DR: The data suggest miRNAs can contribute to changes in macrophage gene expression that occur in different exogenous activating conditions, and can be at least partially explained by repression of TNFAIP3, a negative regulator of NF-κB signaling.

Journal ArticleDOI
TL;DR: This minireview discusses the mechanisms through which S-nitrosylation exerts its broad pleiotropic influence on protein post-translational modification.

Journal ArticleDOI
TL;DR: The overall findings suggest optimum routes to balancing peptide hydrophobicity and charge distribution that allow efficient penetration and disruption of the bacterial membranes without damage to mammalian (host) membranes.

Journal ArticleDOI
TL;DR: It is concluded that the up-regulated HULC by HBx promotes proliferation of hepatoma cells through suppressing p18, which provides new insight into the roles of lncRNAs in HBx-related hepatocarcinogenesis.

Journal ArticleDOI
TL;DR: An autophagy-dependent mechanism of caspase-8 activation and initiation of the apoptotic cascade in response to SKI-I, a pan-sphingosine kinase inhibitor, and bortezomib, a proteasome inhibitor is demonstrated.

Journal ArticleDOI
TL;DR: It is hypothesized that the exosome secretory pathway plays a pleiotropic role in the brain:Exosome secretion is beneficial to the cell, acting as a specific releasing system of neurotoxic APP CTFs and Aβ, but the secretion of exosomes enriched with APP C TFs, neurotoxic proteins that are also a source of secreted Aβ is harmful to the brain.

Journal ArticleDOI
TL;DR: A novel mechanism of apoptosis induction by PAR-4/ceramide-enriched exosomes, which may critically contribute to Alzheimer disease is reported, which is well known to induce neuronal cell death and only little is known about its effect on astrocytes.

Journal ArticleDOI
TL;DR: E3 ubiquitin ligase tripartite motif protein 32 (TRIM32) ubiquitinated MITA and dramatically enhanced MITA-mediated induction of IFN-β and suggest that TRIM32 is an important regulatory protein for innate immunity against both RNA and DNA viruses.

Journal ArticleDOI
TL;DR: The identification and characterization of myonectin are reported, a novel myokine belonging to the C1q/TNF-related protein (CTRP) family, which is a potential nutrient-responsive metabolic regulator secreted by muscle that links skeletal muscle to systemic lipid metabolism via its action on adipocytes and hepatocytes.

Journal ArticleDOI
TL;DR: It is shown that macrophages and neutrophils play distinct functions in tissue regeneration, efficiently resolving inflammation and facilitating tissue remodeling and regrowth.