Atsushi Matsuzawa

Both extra- and intracellular stimuli elicit a wide variety of responses, such as cell survival, proliferation, differentiation, and apoptosis, through regulation of cell signaling. Recent studies have revealed that stress-responsive signal transduction pathways are strictly regulated by the intracellular redox state. The redox state of the cell is a consequence of the precise balance between the levels of oxidizing and reducing equivalents, such as reactive oxygen species (ROS) and endogenous a

Apoptosis, a molecularly regulated form of cell death, is essential for the normal functioning and homeostasis of most multicellular organisms, and can be induced by a range of environmental, physical, and chemical stresses. As the cellular decision to live or to die is made by the coordinated action and balancing of many different pro- and antiapoptotic factors, defects in control of this coordination and balance may contribute to a variety of human diseases, including cancer and autoimmune and

Lysosome rupture triggers NLRP3 inflammasome activation in macrophages. However, the underlying mechanism is not fully understood. Here we showed that the TAK1-JNK pathway, a MAPK signaling pathway, is activated through lysosome rupture and that this activation is necessary for the complete activation of the NLRP3 inflammasome through the oligomerization of an adapter protein, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC). We also revealed that the activat

Cytokine signaling is thought to require assembly of multicomponent signaling complexes at cytoplasmic segments of membrane-embedded receptors, in which receptor-proximal protein kinases are activated. Indeed, CD40, a tumor necrosis factor receptor (TNFR) family member, forms a complex containing adaptor molecules TRAF2 and TRAF3, ubiquitin-conjugating enzyme Ubc13, cellular inhibitor of apoptosis proteins 1 and 2 (c-IAP1/2), IkappaB kinase regulatory subunit IKKgamma (also called NEMO), and mit

Coordination and balance between cell survival and apoptosis is crucial for normal development and homeostasis of multicellular organisms. Defects in control of this balance may contribute to a variety of diseases including cancer, autoimmune and neurodegenerative conditions. Although a large number of pro- and anti-apoptotic factors acting for or against the final death event have been and are being discovered at an extraordinary pace with the recent progress in this area, the molecular mechani

Platelet-activating factor-acetylhydrolase (PAF-AH), which removes the acetyl group at the sn-2 position of PAF, is distributed widely in tissues and plasma. Tissue cytosol contains at least two types of PAF-AH, isoforms Ib and II. Isoform Ib is a tertiary G-protein complex-like heterotrimeric enzyme that is involved in brain development such as formation of the brain cortex. Isoform II (PAF-AH(II)), however, is a 40-kDa monomer and has an amino acid sequence that exhibits a 41% identity with th

Here we show that secretory phospholipase A2 (sPLA2) that is immunochemically indistinguishable from type II sPLA2 is (i) stored in neuroendocrine cells, (ii) released in response to neurotransmitters or depolarization, and (iii) involved in the regulation of catecholamine secretion by these cells. Rat brain synaptic vesicle fractions contained PLA2 activity, which was neutralized completely by an antibody raised against rat type II sPLA2. sPLA2 immunoreactive with anti-(type II sPLA2) antibody

In recent approaches to tissue engineering, cells face various stresses from physical, chemical, and environmental stimuli. For example, coating cell membranes with nanofilms using layer-by-layer (LbL) assembly requires many cycles of centrifugation, causing physical (gravity) stress. Damage to cell membranes can cause the leakage of cytosol molecules or sometimes cell death. Accordingly, we evaluated the effectiveness of LbL films prepared on cell membranes in protecting cells from physical str