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41.
Phalloidin-induced accumulation of myosin in rat hepatocytes is caused by suppression of autolysosome formation 总被引:1,自引:0,他引:1
T Ueno S Watanabe M Hirose T Namihisa E Kominami 《European journal of biochemistry》1990,190(1):63-69
Administration of phalloidin in vivo to rats causes marked changes in the distribution of actin and myosin in hepatocytes, which accompanies reduced bile flow. We have found that in hepatocytes treated with phalloidin for 3 and 7 days, cellular myosin content increased about 1.5-fold and 4.7-fold, respectively. In addition, total cell protein content and several marker enzyme activities were also elevated by 30-120% depending on the duration of phalloidin treatment. These observations allow us to speculate that phalloidin somehow elicits inhibition of cellular protein degradation, which results in the increase of these protein levels. To examine this possibility further, we analyzed leupeptin-induced density shift of phagolysosomes. In normal liver, the injection of leupeptin/E64c caused an increase in the density of both heterolysosomes and autolysosomes, due to retarded digestion of sequestered proteins as a result of the inhibition of lysosomal cathepsins. Accumulation, in these denser autolysosomes, of lactic dehydrogenase, pyruvate kinase, aldolase, and myosin was demonstrated by enzyme assays and immunoblot analysis. In the phalloidin-treated liver, the increase in the density of autolysosomes and the accumulation of above cytoplasmic enzymes were markedly inhibited. However, phalloidin did not affect the shift in the density of heterolysosomes. From these data, we concluded that autolysosome formation was specifically hindered in phalloidin-treated rat hepatocytes, which results in the reduction of autophagic protein degradation and eventual increase in intracellular protein levels. 相似文献
42.
Kenzo Yokozeki Shigeru Yamanaka Koichi Takinami Yoshio Hirose Atsuo Tanaka Kenji Sonomoto Saburo Fukui 《Applied microbiology and biotechnology》1982,14(1):1-5
Summary Lipase from Rhizopus delemar was immobilized by entrapment with photo-crosslinkable resin prepolymers or urethane prepolymers or by binding to various types of porous silica beads. The immobilized lipase preparations thus obtained were examined for their activity in converting olive oil to an interesterified fat (cacao butter-like fat), whose oleic acid moieties at 1- and 3-positions were replaced with stearic acid moieties, in the reaction solvent n-hexane. Although all of the immobilized preparations exhibited some activity, lipase adsorbed on Celite and then entrapped with a hydrophobic photo-crosslinkable resin prepolymer showed the highest activity, about 75% of that of lipase simply adsorbed onto Celite. Entrapment markedly enhanced the operational stability of lipase.Dedicated to Professor H. Holzer, Freiburg University, on his 60th birthday (June 13, 1981) 相似文献
43.
44.
M Kitada K Igarashi S Hirose H Kitagawa 《Biochemical and biophysical research communications》1979,87(2):388-394
Both NADPH- and ascorbic acid-dependent lipid peroxidations were inhibited by spermine, the degree of inhibition being greater with the former peroxidation. The effective concentration of spermine required for inhibition was higher when larger amounts of microsomes were used. However, the activities of NADPH-cytochrome c reductase and NADPH-peroxidase were not influenced by spermine. These results suggest that spermine inhibits lipid peroxidation by binding to phospholipids in the microsomes. 相似文献
45.
K Igarashi M Tanaka K Eguchi S Hirose 《Biochemical and biophysical research communications》1978,83(1):274-280
It is shown that rat liver isoleucyl-tRNA formation in the presence of Mg2+ is inhibited by poly(G), poly(I) or ribosomes and that this inhibition is prevented by polyamines. The inhibition is found to be noncompetitive with respect to tRNA. 相似文献
46.
K Igarashi H Kumagai Y Watanabe N Toyoda S Hirose 《Biochemical and biophysical research communications》1975,67(3):1070-1077
The activities of ribonucleases (RNase HS and RNase A), which hydrolyze ribonucleic acid at linkages attached to pyrimidine nucleotides were stimulated by polyamines, while the activities of ribonucleases (RNase T1 and RNase M), which attack ribonucleic acid at linkages attached to purine nucleotides were not influenced by polyamines. In the presence of polyamines, the cleavage of C5′-O-P linkages adjacent to cytosine nucleotide was stimulated, while the cleavage of C5′-O-P linkages adjacent to uracil nucleotides was inhibited slightly. The effect of polyamines on the activities of ribonucleases occured through the binding of the polyamines to nucleic acid. 相似文献
47.
48.
Mahabub Alam Hiroki Shima Yoshitaka Matsuo Nguyen Chi Long Mitsuyo Matsumoto Yusho Ishii Nichika Sato Takato Sugiyama Risa Nobuta Satoshi Hashimoto Liang Liu Mika K. Kaneko Yukinari Kato Toshifumi Inada Kazuhiko Igarashi 《The Journal of biological chemistry》2022,298(7)
Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (SAM). As the sole methyl-donor for methylation of DNA, RNA, and proteins, SAM levels affect gene expression by changing methylation patterns. Expression of MAT2A, the catalytic subunit of isozyme MAT2, is positively correlated with proliferation of cancer cells; however, how MAT2A promotes cell proliferation is largely unknown. Given that the protein synthesis is induced in proliferating cells and that RNA and protein components of translation machinery are methylated, we tested here whether MAT2 and SAM are coupled with protein synthesis. By measuring ongoing protein translation via puromycin labeling, we revealed that MAT2A depletion or chemical inhibition reduced protein synthesis in HeLa and Hepa1 cells. Furthermore, overexpression of MAT2A enhanced protein synthesis, indicating that SAM is limiting under normal culture conditions. In addition, MAT2 inhibition did not accompany reduction in mechanistic target of rapamycin complex 1 activity but nevertheless reduced polysome formation. Polysome-bound RNA sequencing revealed that MAT2 inhibition decreased translation efficiency of some fraction of mRNAs. MAT2A was also found to interact with the proteins involved in rRNA processing and ribosome biogenesis; depletion or inhibition of MAT2 reduced 18S rRNA processing. Finally, quantitative mass spectrometry revealed that some translation factors were dynamically methylated in response to the activity of MAT2A. These observations suggest that cells possess an mTOR-independent regulatory mechanism that tunes translation in response to the levels of SAM. Such a system may acclimate cells for survival when SAM synthesis is reduced, whereas it may support proliferation when SAM is sufficient. 相似文献
49.
Kannoa T Kanatani A Keen SL Arai-Otsuki S Haga Y Iwama T Ishihara A Sakuraba A Iwaasa H Hirose M Morishima H Fukami T Ihara M 《Peptides》2001,22(3):405-413
The peptidic Y1 antagonist 1229U91 and the non-peptidic antagonist J-104870 have high binding affinities for the human Y1 receptor. These Y1 antagonists show anorexigenic effects on NPY-induced feeding in rats, although they have completely different structures and molecular sizes. To identify the binding sites of these ligands, we substituted amino acid residues of the human Y1 receptor with alanine and examined the abilities of the mutant receptors to bind the radio-labeled ligands. Alanine substitutions, F98A, D104A, T125A, D200A, D205A, L215A, Q219A, L279A, F282A, F286A, W288A and H298A, in the human Y1 receptor lost their affinity for the peptide agonist PYY, but not for 1229U91 and J-104870, while L303A and F173A lost affinity for 1229U91 and J-104870, respectively. N283A retained its affinity for 1229U91, but not for PYY and J-104870. Y47A and N299A retained their affinity for J-104870, but not for PYY and 1229U91. W163A and D287A showed no affinity for any of the three ligands. Taken together, these data indicate that the binding sites of 1229U91 are widely located in the shallow region of the transmembrane (TM) domain of the receptor, especially TM1, TM6 and TM7. In contrast, J-104870 recognized the pocket formed by TM4, TM5 and TM6, based on the molecular modeling of the Y1 receptor and J-104870 complex. In conclusion, 1229U91 and J-104870 have high affinities for Y1 receptors using basically different binding sites. D287 of the common binding site in the TM6 domain could be crucial for the binding of Y1 antagonists. 相似文献
50.
Yoshitaka Shimizu Shinjiro Todo Shinsaku Imashuku 《Prostaglandins & other lipid mediators》1986,32(4)
To study the precise mechanism of cytotoxic activity of PGD2 or Δ12-PGJ2 (a biological active metabolite of PGD2), we examined the effect of various compounds on PGD2 or Δ12-PGJ2 cytottoxic, using a human neuroblastoma cell line (NCG). Cycloheximide (CHM) specifically protected PGD2 cytotoxicity on NCG cells. When Δ12-PGJ2 was tested, CHM exhibited a similar rescue effect. Puromycin, mitomycin C, and α-amanitin did not affect PGD2 or Δ12-PGJ2 cytotoxicity. Emetine showed a variable and no consistent rescue effect CHM may have been active at the primary site where PGD2 or Δ12-PGJ2 exerts its cytotoxicity. This is the first report indicating that CHM reduces the cytotoxicity induced by PGD2 or Δ12-PGJ2. 相似文献