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Pseudoapoptosis can be defined from multiple viewpoints, with an underlying premise of the differences in cellular processes and states relating to apoptosis. Pseudoapoptosis can be referred to as an apoptotic-like cellular state that can be readily reversed.〔Annmarie Surprenant, et al. "Pseudoapoptosis Induced By Brief Activation Of ATP-Gated P2X7 Receptors." Journal Of Biological Chemistry 280.40 (2005): 33968-33976〕 , or as a process that induces rapid apoptosis through the introduction of drugs such as bleomycin.〔Vorobjev, Pavel, Olessia Tchaika, and Valentina Zarytova. "Efficient Cleavage Of DS DNA By Bleomycin Conjugated Via Hexaethylene Glycol Linker To Triplex-Forming Oligonucleotides." Nucleosides, Nucleotides & Nucleic Acids 23.6/7 (2004): 1047-1051.〕 Pseudoapoptosis has been used to define a cellular state closely resembling the initial stages of apoptosis, but asserts a readily reversible state of which a cell can resume normal cellular function. Chemical and morphological changes morphology- a cell may undergo associated with pseudoapoptosis include blebbing, plasma membrane lipid asymmetry cell membrane, cytoskeleton alterations cytoskeleton, mitochondrial function mitochondria, and increased concentration of cytosolic calcium. Regardless of these cellular alterations, pseudoapoptotic cells reverse these changes to resume normal cellular process.〔Annmarie Surprenant, et al. "Pseudoapoptosis Induced By Brief Activation Of ATP-Gated P2X7 Receptors." Journal Of Biological Chemistry 280.40 (2005): 33968-33976〕 Pseudoapoptosis has also been used in some instances when describing an accelerated, drug induced apoptotic pathway by bleomycin. Cell death occurs as it would in apoptosis, but certain apoptotic mechanisms are not utilized when in the presence of bleomycin.〔L M Mir, et al. "The Ratio Of Single- To Double-Strand DNA Breaks And Their Absolute Values Determine Cell Death Pathway." British Journal Of Cancer 84.9 (2001): 1272 〕〔L M Mir, et al. "In Vivo Evolution Of Tumour Cells After The Generation Of Double-Strand DNA Breaks." British Journal Of Cancer 88.11 (2003): 1763. 〕 ==Bleomycin== Bleomycin (BLM) is a cytotoxic, anticancerous drug that catalyzes double-stranded breaks (DSB) and single-stranded breaks (SSB) along DNA molecules. BLM has four distinguishable molecular components that determine function, including a DNA-binding region, metal binding domain, linker region, and a carbohydrate moiety. The metal binding domain associates with metals such as iron, cobalt, and zinc, each provides the basis of selectivity towards interaction with specific regions of DNA for catalytic cleavage. It is believed that the catalytic activity of BLM is carried out by associating with DNA molecules in linker regions between nucleosomes. Specific nucleotide sequences within the minor groove of a DNA molecule are a primary target as a catalytic site.〔Vorobjev, Pavel, Olessia Tchaika, and Valentina Zarytova. "Efficient Cleavage Of DS DNA By Bleomycin Conjugated Via Hexaethylene Glycol Linker To Triplex-Forming Oligonucleotides." Nucleosides, Nucleotides & Nucleic Acids 23.6/7 (2004): 1047-1051.〕 At appropriate dosages, BLM generates morphological changes resembling typical apoptotic events, such as membrane blebbing and altered mitochondrial functioning. Degradation of DNA is also induced without the presence or assistance of specific endonuclease or protease that are involved under classic apoptotic conditions, which defines the usage of this form of pseudoapoptosis.〔L M Mir, et al. "In Vivo Evolution Of Tumour Cells After The Generation Of Double-Strand DNA Breaks." British Journal Of Cancer 88.11 (2003): 1763.〕 The relative dose administered determines the extent to which DNA fragmentation occurs. In the presence of large BLM concentrations, pseudoapoptosis is observed as rapid DNA fragmentation occurs, resulting in cell death in the absence of typical apoptotic components such as specific endonucleases and proteases.〔L M Mir, et al. "In Vivo Evolution Of Tumour Cells After The Generation Of Double-Strand DNA Breaks." British Journal Of Cancer 88.11 (2003): 1763〕 Experimental evidence has suggested that every BLM molecule induces an average of 8 to 10 DNA strand breaks. An average ratio of 6 single-stranded breaks are generated for every double-stranded break. These numbers are dependent upon the form of BLM taken into consideration as deglyco-bleomycin has been found to be 100 times less toxic than wild-type BLM. Other forms of BLM forming complexes with various metals has suggested other variability when inducing pseudoapoptosis.〔L M Mir, et al. "The Ratio Of Single- To Double-Strand DNA Breaks And Their Absolute Values Determine Cell Death Pathway." British Journal Of Cancer 84.9 (2001): 1272〕 抄文引用元・出典: フリー百科事典『 ウィキペディア(Wikipedia)』 ■ウィキペディアで「Pseudoapoptosis」の詳細全文を読む スポンサード リンク
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