Requirements of an IκB-βC-terminus protein for the acidic adaptation in mammalian cells   :   哺乳動物細胞の耐酸性におけるIκB-βC末端タンパクの必要性 

作成者 Lao, Qizong
作成者の別表記 老, 啓宗
キーワード等 acidic adaptation, IκB, 耐酸性
日本十進分類法 (NDC) 490
内容 抄録:Together with hypoxia and low nutrient, low pH has been identified as a major property of solid tumor tissue. Cells maintain intracellular pH (pHi) homeostasis and proliferate under this acidic stress regardless it is considered that weak alkali or neutral environmental pH (pHe) is essential for the functions and proliferation of mammalian cells. Although it has been reported previously that Na^+/H^+ exchangers, HCO_<3^-> (co) transporters and H^+ -ATPases function in maintenance of pHi homeostasis, the overall mechanisms underlie the acidic adaptation in mammalian cells remain unclear because previous studies always focused on the cytosol alkalinization of cells cultured in neutral environments and then subjected to artificial cytosol acidification, but not on the adaptation of cells cultured in acidic environments. Since acidic adaptation is a very complex process, it is reasonable to consider that besides those known pHi regulatory mechanisms, there are other mechanisms involved. In order to identify and investigate those unknown mechanisms of acidic adaptation, serial trials were initiated with Chinese Hamster Ovary (CHO-K1) cells in this study. CHO-K1 was able to proliferate and maintain pHi homeostasis in acidic media with pH values as low as 6.3. Among those known pHi regulatory mechanisms, only Na^+/H^+ exchangers played partial roles in maintenance of pHi homeostasis under acidic conditions. A novel acidic-sensitive mutant designated AS-5B, which proliferated in neutral and weak alkali environments but failed to proliferate or maintain pHi homeostasis in acidic environments, was derived from CHO-K1 by using a replica strategy. The acidic-sensitivity of AS-5B was not due to the deficiency in the known pHi regulatory mechanisms. A cDNA clone conferring partial acidic-resistance on AS-5B was also isolated. The encoded protein contained only the COOH terminal region of IκB-βand it was therefore designated CTIB (COOH Terminal region of IκB

コンテンツの種類 博士論文 Doctoral Thesis
DCMI資源タイプ text
ファイル形式 application/pdf
言語 英語

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