The nerve axon is a good model system for studying the molecular mechanism of organelle transport in cells. Recently, new kinesin superfamily proteins (KIFs) have been identified as candidate motor involved transport. Among them KIF1A, murine homologue unc-104 gene Caenorhabditis elegans, unique monomeric neuron– specific microtubule plus end–directed and has proposed transporter synaptic vesicle precursors (Okada, Y., H. Yamazaki, Y. Sekine-Aizawa, N. Hirokawa. 1995. Cell. 81:769–780). To...

In mature neurons, tau is abundant in axons, whereas microtubule-associated protein 2 (MAP2) and MAP2C are specifically localized dendrites. Known mechanisms involved the compartmentalization of these cytoskeletal proteins include differential localization mRNA (MAP2 dendrites, cell body, Tau proximal axon revealed by situ hybridization) (Garner, C.C., R.P. Tucker, A. Matus. 1988. Nature (Lond.). 336:674-677; Litman, P., J. Barg, L. Rindzooski, I. Ginzburg. 1993. Neuron. 10:627-638),...

Sepsis/endotoxemia is elicited by the circulatory distribution of pathogens/endotoxins into whole bodies, and causes profound effects on human health causing inflammation in multiple organs. Mitochondrial damage one characteristics cellular degeneration observed during sepsis/endotoxemia. Elimination damaged mitochondria through autophagy-lysosome system has been reported liver, indicating that autophagy should play an important role liver homeostasis An increased appearance mitochondrial...

Pyroptosis, a type of inflammatory cell death, is dependent on the caspase-mediated cleavage gasdermin D (GSDMD), and subsequent pore formation plasma membranes through which interleukin (IL)-1β IL-18 are released from cells. During proinflammatory activation, macrophages shift their metabolism aerobic oxidative phosphorylation to anaerobic glycolysis. Hypoxia-inducible factor (HIF)1α involved in induction IL-1β gene expression as well metabolic towards However, relationships between...

IL-12 is a heterodimeric cytokine composed of two covalently linked chains, p40 and p35. expression appears to be restricted monocytes/macrophages B cells highly regulated, while p35 more ubiquitously constitutively expressed. To investigate the mechanism involved in regulation expression, we molecularly cloned characterized murine genes. The gene spans over 14 kb, consists eight exons seven introns, was shown localized on chromosome 11A5-B2 by fluorescence situ hybridization. A single major...

The aim of this study is to investigate the molecular mechanisms underlying delayed progressive pulmonary fibrosis, a characteristic subacute paraquat (PQ) poisoning. Epithelial-mesenchymal transition (EMT) has been proposed as cause organ and transforming growth factor-β (TGF-β) suggested be powerful mediator EMT. We thus examined possibility that EMT involved in fibrosis during PQ poisoning using A549 human alveolar epithelial cells vitro. were treated with various concentrations (0–500...

Lipopolysaccharide (LPS)-induced myocardial dysfunction is caused, at least in part, by mitochondrial dysfunction. Mitochondrial and the oxidative damage associated with it are scavenged through various cellular defense systems such as autophagy to prevent harmful effects. Our recent study has demonstrated that cobalt protoporphyrin IX (CoPPIX), a potent inducer of heme oxygenase-1 (HO-1), ameliorates septic liver injuries enhancing rats. In our current study, we show CoPPIX (5 mg/kg s.c.)...

Neurofilaments (NFs) are composed of triplet proteins, NF-H, NF-M, and NF-L. To understand the dynamics NFs in vivo, we studied NF-H compared them to those NF-L, using combination microinjection technique fluorescence recovery after photobleaching. In case NF-L protein, bleached zone gradually restored its intensity with a half time approximately 35 min. On other hand, was considerably faster, taking place 19 However, both cases stationary. Thus, it suggested that is dynamic component NF...

The mechanism of cytoskeletal protein transport, especially the question what kind form proteins assume during transport in neurons situ, has been an important, as yet unsettled issue. To clear up this matter, we adopted embryonic zebrafish a living animal model and applied fluorescence recovery after photobleaching (FRAP) method. embryo is appropriate for study because its transparency early developmental stage, allowing observation that incorporate microinjected fluorescent tubulin...

Mitochondrial damage and subsequent oxidative stresses play important roles in the pathogenesis of sepsis-induced organ failure. Recently, autophagy, major degradation pathway involved mitochondrial quality control, was reported as a cellular adaptive response to stresses. The aim present study elucidate molecular mechanism that underlies hepatic during lipopolysaccharide (LPS) treatment. We also try determine if can be attenuated by administration cobalt protoporphyrin (CoPP), potent heme...

Aberrant cellular accumulation of cholesterol is associated with neuronal lysosomal storage disorders such as Niemann-Pick disease Type C (NPC). We have shown previously that l-norephedrine (l-Nor), a sympathomimetic amine, induces necrotic cell death massive cytoplasmic vacuolation in SH-SY5Y human neuroblastoma cells. To reveal the molecular mechanism underling caused by l-Nor, we examined alterations gene expression profile cells during l-Nor exposure. DNA microarray analysis revealed...

In order to determine the amino‐terminal sequence requirements for protein N‐myristoylation, site‐directed mutagenesis of N‐terminal region was performed using tumor necrosis factor (TNF) mutants as model substrate proteins. Subsequently, susceptibility these N‐myristoylation evaluated by metabolic labeling in an vitro translation system rabbit reticulocyte lysate. A TNF mutant having MGAAAAAAAA at its N‐terminus used starting identify elements critical N‐myristoylation. Sequential...

To determine whether tubulin molecules transported in axons are polymers or oligomers, we carried out electron microscopic analysis of the movement after photoactivation. Although previous optical analyses photobleaching photoactivation had suggested that most axonal microtubules were stationary, they not sufficiently sensitive to allow detection actively which expected be only a small fraction total axons. In addition, some recent studies using indirect approaches active polymer transport...