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121.
Mamunur Rashid Mahib Shoko Hosojima Hiroko Kushiyama Takeshi Kinoshita Toshihiko Shiroishi Takashi Suda Kohsuke Tsuchiya 《Microbiology and immunology》2020,64(2):143-152
Inflammasomes are innate immune mechanisms that activate caspase-1 in response to a variety of stimuli, including Salmonella infection. Active caspase-1 has a potential to induce two different types of cell death, depending on the expression of the pyroptosis mediator gasdermin D (GSDMD); following caspase-1 activation, GSDMD-sufficient and GSDMD-null/low cells undergo pyroptosis and apoptosis, respectively. Although Bid, a caspase-1 substrate, plays a critical role in caspase-1 induction of apoptosis in GSDMD-null/low cells, an additional mechanism that mediates this cell death independently of Bid has also been suggested. This study investigated the Bid-independent pathway of caspase-1-induced apoptosis. Caspase-1 has been reported to process caspase-6 and caspase-7. Silencing of caspase-7, but not caspase-6, significantly reduced the activation of caspase-3 induced by caspase-1, which was activated by chemical dimerization, in GSDMD/Bid-deficient cells. CRISPR/Cas9-mediated depletion of caspase-7 had the same effect on the caspase-3 activation. Moreover, in the absence of GSDMD and Bid, caspase-7 depletion reduced apoptosis induced by caspase-1 activation. Caspase-7 was activated following caspase-1 activation independently of caspase-3, suggesting that caspase-7 acts downstream of caspase-1 and upstream of caspase-3. Salmonella induced the activation of caspase-3 in GSDMD-deficient macrophages, which relied partly on Bid and largely on caspase-1. The caspase-3 activation and apoptotic morphological changes seen in Salmonella-infected GSDMD/Bid-deficient macrophages were attenuated by caspase-7 knockdown. These results suggest that in addition to Bid, caspase-7 can also mediate caspase-1-induced apoptosis and provide mechanistic insights into inflammasome-associated cell death that is one major effector mechanism of inflammasomes. 相似文献
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Masahiko Idei Keigo Osada Shinya Sato Takeshi Nakayama Tamotsu Nagumo David G. Mann 《Protoplasma》2013,250(4):833-850
The most complete account to date of the ultrastructure of flagellate cells in diatoms is given for the sperm of Thalassiosira lacustris and Melosira moniliformis var. octogona, based on serial sections. The sperm are uniflagellate, with no trace of a second basal body, and possess a 9?+?0 axoneme. The significance of the 9?+?0 configuration is discussed: lack of the central pair microtubules and radial spokes does not compromise the mastigoneme-bearing flagellum’s capacity to perform planar beats and thrust reversal and may perhaps be related to sensory/secretory function of the sperm flagellum during plasmogamy. The basal bodies of diatoms are confirmed to contain doublets rather than triplets, which may correlate with the absence of some centriolar proteins found in most cells producing active flagella. Whereas Melosira possesses a normal cartwheel structure in the long basal body, no such structure is present in Thalassiosira, which instead possesses ‘intercalary fibres’ linking the basal body doublets. No transitional helices or transitional plates are present in either species studied. Cones of microtubules are associated with the basal body and partially enclose the nucleus in M. moniliformis and T. lacustris. They do not appear to be true microtubular roots and may arise through transformation of the meiosis II spindle. A close association between cone microtubules and tubules containing mastigonemes may indicate a function in intracellular mastigoneme transport. No correlation can yet be detected between methods of spermatogenesis and phylogeny in diatoms, contrary to previous suggestions. 相似文献
124.
Toshiaki Nakano Mayumi Miyamoto-Matsubara Mahmoud I. Shoulkamy Amir M. H. Salem Seung Pil Pack Yukio Ishimi Hiroshi Ide 《The Journal of biological chemistry》2013,288(7):4649-4658
DNA-protein cross-links (DPCs) are formed when cells are exposed to various DNA-damaging agents. Because DPCs are extremely large, steric hindrance conferred by DPCs is likely to affect many aspects of DNA transactions. In DNA replication, DPCs are first encountered by the replicative helicase that moves at the head of the replisome. However, little is known about how replicative helicases respond to covalently immobilized protein roadblocks. In the present study we elucidated the effect of DPCs on the DNA unwinding reaction of hexameric replicative helicases in vitro using defined DPC substrates. DPCs on the translocating strand but not on the nontranslocating strand impeded the progression of the helicases including the phage T7 gene 4 protein, simian virus 40 large T antigen, Escherichia coli DnaB protein, and human minichromosome maintenance Mcm467 subcomplex. The impediment varied with the size of the cross-linked proteins, with a threshold size for clearance of 5.0–14.1 kDa. These results indicate that the central channel of the dynamically translocating hexameric ring helicases can accommodate only small proteins and that all of the helicases tested use the steric exclusion mechanism to unwind duplex DNA. These results further suggest that DPCs on the translocating and nontranslocating strands constitute helicase and polymerase blocks, respectively. The helicases stalled by DPC had limited stability and dissociated from DNA with a half-life of 15–36 min. The implications of the results are discussed in relation to the distinct stabilities of replisomes that encounter tight but reversible DNA-protein complexes and irreversible DPC roadblocks. 相似文献
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127.
Fumiaki Nakayama Sachiko Umeda Tomomi Ichimiya Shin Kamiyama Masaharu Hazawa Takeshi Yasuda Shoko Nishihara Takashi Imai 《FEBS letters》2013,587(2):231-237
This study focuses on clarifying the contribution of sulfation to radiation-induced apoptosis in human Burkitt’s lymphoma cell lines, using 3′-phosphoadenosine 5′-phosphosulfate transporters (PAPSTs). Overexpression of PAPST1 or PAPST2 reduced radiation-induced apoptosis in Namalwa cells, whereas the repression of PAPST1 expression enhanced apoptosis. Inhibition of PAPST slightly decreased keratan sulfate (KS) expression, so that depletion of KS significantly increased radiation-induced apoptosis. In addition, the repression of all three N-acetylglucosamine-6-O-sulfotransferases (CHST2, CHST6, and CHST7) increased apoptosis. In contrast, PAPST1 expression promoted the phosphorylation of p38 MAPK and Akt in irradiated Namalwa cells. These findings suggest that 6-O-sulfation of GlcNAc residues in KS reduces radiation-induced apoptosis of human Burkitt’s lymphoma cells. 相似文献
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129.
Chisato Kusunoki Liu Yang Takeshi Yoshizaki Fumiyuki Nakagawa Atsushi Ishikado Motoyuki Kondo Katsutaro Morino Osamu Sekine Satoshi Ugi Yoshihiko Nishio Atsunori Kashiwagi Hiroshi Maegawa 《Biochemical and biophysical research communications》2013,430(1):225-230
Oxidative stress is produced in adipose tissue of obese subjects and has been associated with obesity-related disorders. Recent studies have shown that omega-3 polyunsaturated fatty acid (ω3-PUFA) has beneficial effects in preventing atherosclerotic diseases and insulin resistance in adipose tissue. However, the role of ω3-PUFA on adipocytes has not been elucidated. In this study, 3T3-L1 adipocytes were treated with ω3-PUFA and its metabolites, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or 4-hydroxy hexenal (4-HHE). ω3-PUFA and its metabolites dose-dependently increased mRNA and protein levels of the anti-oxidative enzyme, heme oxygenase-1 (HO-1); whereas no changes in the well-known anti-oxidant molecules, superoxide dismutase, catalase, and glutathione peroxidase, were observed. Knockdown of nuclear factor erythroid 2-related factor 2 (Nrf-2) significantly reduced EPA, DHA or 4-HHE-induced HO-1 mRNA and protein expression. Also, pretreatment with ω3-PUFA prevented H2O2-induced cytotoxicity in a HO-1 dependent manner. In conclusion, treatment with EPA and DHA induced HO-1 through the activation of Nrf-2 and prevented oxidative stress in 3T3-L1 adipocytes. This anti-oxidant defense may be of high therapeutic value for clinical conditions associated with systemic oxidative stress. 相似文献
130.
Elisa Tran Annabelle Chow Takeshi Goda Amy Wong Kim Blakely Michelle Rocha Samira Taeb Van C. Hoang Stanley K. Liu Urban Emmenegger 《Biochemical and biophysical research communications》2013
ATG4B belongs to the autophagin family of cysteine proteases required for autophagy, an emerging target of cancer therapy. Developing pharmacological ATG4B inhibitors is a very active area of research. However, detailed studies on the role of ATG4B during anticancer therapy are lacking. By analyzing PC-3 and C4-2 prostate cancer cells overexpressing dominant negative ATG4BC74Ain vitro and in vivo, we show that the effects of ATG4BC74A are cell type, treatment, and context-dependent. ATG4BC74A expression can either amplify the effects of cytotoxic therapies or contribute to treatment resistance. Thus, the successful clinical application of ATG4B inhibitors will depend on finding predictive markers of response. 相似文献