Hirai H, Natori S, Sekimizu K
Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Biochim Biophys Acta. 1991 Feb 16;1088(2):191-6. doi: 10.1016/0167-4781(91)90054-p.
Drugs with affinity for phospholipids, such as chlorpromazine, verapamil, tetracaine and imipramine, were found to inhibit accurate transcription from adenovirus 2 major late promoter in a nuclear extract of Ehrlich ascites tumor cells. The transcription activity of the nuclear extract inhibited by chlorpromazine was restored by addition of acidic phospholipids. The nuclear extract was also shown to lose transcription activity when treated with phospholipase A2. Chlorpromazine was found to inhibit transcription at the step of initiation, not elongation. Moreover, it did not affect the activity of purified RNA polymerase II, suggesting the interaction of phospholipids with transcription factors in the nuclear extract. Some transcription factors in the nuclear extract were found to have affinity for cardiolipin, and were precipitated with excess cardiolipin. The transcription factors precipitated with cardiolipin could be solubilized with guanidine hydrochloride, and restored the transcription activity of the cardiolipin-treated nuclear extract.
已发现对磷脂具有亲和力的药物，如氯丙嗪、维拉帕米、丁卡因和丙咪嗪，能在艾氏腹水瘤细胞核提取物中抑制腺病毒2主要晚期启动子的精确转录。氯丙嗪抑制的核提取物的转录活性可通过添加酸性磷脂来恢复。当用磷脂酶A2处理时，核提取物也显示出失去转录活性。发现氯丙嗪在起始步骤而非延伸步骤抑制转录。此外，它不影响纯化的RNA聚合酶II的活性，这表明磷脂与核提取物中的转录因子相互作用。发现核提取物中的一些转录因子对心磷脂具有亲和力，并可被过量的心磷脂沉淀。用盐酸胍可使与心磷脂沉淀的转录因子溶解，并恢复经心磷脂处理的核提取物的转录活性。
