Detail Mechanism of programmed cell death in murine macrophages cell line PU5-1.8 Bibliografi Author: Suen, Yick Keung ; Ho, K. K. (Advisor) Topik: BIOLOGY; CELL|BIOLOGY; MOLECULAR Bahasa: (EN )    ISBN: 0-599-55374-X     Penerbit: CHINESE UNIVERSITY OF HONG KONG (PEOPLE'S REPUBLIC OF CHINA)     Tahun Terbit: 1999     Jenis: Theses - Dissertation Fulltext: 9951505.pdf (0.0B; 2 download) Abstract Cell death can be divided into two categories: necrosis and apoptosis. Necrosis is a passive process and is always a result of cell injury, while apoptosis is an active process with the existence of a ‘suicide programme’. Apoptotic death is the physiological process which control the homeostasis of the body by (1) sculpting of body parts; (2) deleting unwanted structures; (3) controlling cell numbers such as the development of nervous system; and (4) eliminating nonfunctional and harmful cells. In the present study, the mechanism controlling apoptosis in macrophages was investigated with the use of plant lectin Concanavalin A (Con A) and fungal toxin gliotoxin (GT). The fact that macrophages play an important role in many disease states raise the possibility that the removal of macrophages activities as a cure of the diseases and the understanding of the apoptosis controlling pathways may provide new idea for therapy of those diseases. Concanavalin A (Con A) is a lectin which was found to be a mitogen in lymphocytes and an activator in macrophages. The effect of Con A on PU5-1.8 cells was further demonstrated in the production of DNA fragmentation and phosphatidylserine (PS) exposure, and hence Con A induced apoptosis in PU5-1.8 cells. Con A bind on cell surface receptor and internalized into the cells. After that, they localized near mitochondria and also lead to clustering of the organelles. This binding of Con A to mitochondria was proved to stimulate the release of cyto c, which may then initiate the process of apoptosis. Gliotoxin (GT) is one of the well-known members of the epipolythiodioxopiperazine (ETP) class of fungal toxins, and specifically affect cells in immune systems. GT was shown to induce apoptosis in PU5-1.8 cells in a dose dependent manner. Apoptosis induced by GT is cell cycle independent when assayed by TUNEL method. GT generated H2O2 and also hydroethidine sensitive ROS intracellularly. Though there is no change in mitochondrial membrane potential during GT treatment, cyto c still released to the cytosol. However, the cyto c dependent pathway is not the only controlling system for GT mediated apoptosis. In fact, the presence of H2O2 would inhibit the cyto c dependent apoptotic effect. Endonuclease responsible for the DNA fragmentation during apoptosis was investigated. Nuclease activities were found in nuclei of untreated PU5-1.8 cells. The activity was identified as a DNase I like enzyme with molecular weight similar to DNase I and was effectively inhibited by the DNase I inhibitor—actin. After treatment of PU5-1.8 cells with GT, there is changes in the chromosome structure, which is more susceptible for the degradation by endonuclease. Dexamethasone (Dex) is a synthetic glucocorticord hormone and was shown to induced apoptosis in thymocytes. However, it also an anti-apoptotic agent in monocytes, neutrophils and PU5-1.8 cells. The effect of Dex seems to be the result of change in the Bcl-2 family proteins. Hence it is suggested that Dex increase the level of anti-apoptotic protein Bcl- XL and decrease the level of pro-apoptotic protein Bad. Opini Anda Klik untuk menuliskan opini Anda tentang koleksi ini! Lihat Sejarah Pengadaan  Konversi Metadata   Kembali

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