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[氯喹和柔红霉素在L细胞(LSM亚系)中的分离与积累对溶酶体水解酶活性的影响]

[Effect of the segregation and accumulation of chloroquine and daunorubicin by L cells (LSM subline) on the activity of lysosomal hydrolases].

作者信息

Bulychev A G, Semenova E G, Assinovskaia O A, Prozorovskaia M P

出版信息

Tsitologiia. 1988 May;30(5):560-7.

PMID:3176170
Abstract

Kinetics of chloroquine and daunorubicin (DNR) uptake by cultured L cells (subline LSM) has been studied. With their constant concentrations in the medium the uptake of both chloroquine and DNR was characterized as a two phase process. Within 1.5-2 hours, these cells accumulated as much as 90 per cent of the total chloroquine and DNR amounts taken up during the whole incubation period. The segregation and accumulation of these substances took place in lysosomes. Chloroquine and DNR concentrations within lysosomes exceed those in the medium by 1100 and 5000 times, respectively. The chloroquine and DNR accumulation in lysosomes inhibited activities of some lysosomal hydrolases tested: cathepsins B and D, N-acetyl-beta, D-glucosaminidase and acid phosphatase. Unlike, the activity of acid lipase was not affected by chloroquine, and was sufficiently stimulated (by 55%) by DNR. The mechanism of inhibition of lysosomal enzymes by chloroquine and DNR is not yet known, although some suggestions are made. Possible consequences of lysosomal activity inhibition for cell metabolism are discussed in addition to a possible role of lysosomotropic agents as regulators of lysosomal functional activity.

摘要

已对培养的L细胞(LSM亚系)摄取氯喹和柔红霉素(DNR)的动力学进行了研究。在培养基中它们的浓度保持恒定的情况下,氯喹和DNR的摄取均表现为一个两阶段过程。在1.5 - 2小时内,这些细胞积累了整个孵育期摄取的氯喹和DNR总量的90%。这些物质的分离和积累发生在溶酶体中。溶酶体内氯喹和DNR的浓度分别比培养基中的浓度高1100倍和5000倍。溶酶体中氯喹和DNR的积累抑制了所检测的一些溶酶体水解酶的活性:组织蛋白酶B和D、N - 乙酰 - β - D - 氨基葡萄糖苷酶和酸性磷酸酶。不同的是,酸性脂肪酶的活性不受氯喹影响,而被DNR充分刺激(提高55%)。虽然提出了一些推测,但氯喹和DNR抑制溶酶体酶的机制尚不清楚。除了溶酶体促渗剂作为溶酶体功能活性调节剂的可能作用外,还讨论了溶酶体活性抑制对细胞代谢的可能后果。

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