Chinese hamster ovary cell variants resistant to monensin, an ionophoric antibiotic. I. Isolation and altered endocytosis of ricin

✍ Scribed by Mayumi Ono; Hisae Yamato; Miho Ando; Michihiko Kuwano

• Publisher: John Wiley and Sons
• Year: 1984
• Tongue: English
• Weight: 567 KB
• Volume: 119
• Category: Article
• ISSN: 0021-9541
• DOI: 10.1002/jcp.1041190209

✦ Synopsis

Chinese hamster ovary (CHO) cell variants resistant to a carboxylic ionophore, monensin, have been isolated. Two monensin-resistant variants and Mon ' -32) showed a threeto fourfold higher resistance to monensin than did CHO. These Mon' clones also showed fourfold higher resistance to another carboxylic ionophore, nigericin, and twofold higher resistance to valinomycin. They were also slightly more resistant to other unrelated drugs such as adriamycin, colchicine, bleomycin, and chloroquine, and in particular, they showed about threefold higher resistance to ricin, a toxin of Ricinus communis. MonR clones were found to retain a normal level of [1251]ricin binding, but internalization of [1251]ricin into the MonR clones was one-half or less than with CHO. Present data suggest that drug-resistant clones selected in culture may provide a way to isolate cells with altered response to various bioactive molecules.

Monensin and negericin are carboxylic ionophores for Na+ and K+, which inhibit proton gradients by electroneutral transmembrane exchange of protons for monovalent cations (Pressman 1976). Thus they show pleiotropic effects on mammalian cells. The ionophores were first shown to inhibit protein secretion by Tartakoff and Vassalli (Tartakoff and Vassalli, 1977, 1978); the cytoplastic Na+/Kf balance at the Golgi level has been suggested to be involved in the intracellular transport of secretory products. Many studies with monensin indicate that drug causes a variety of biological effects, including an inhibition of pinocytosis (Wilcox et al., 1982), inhibition of recycling of low-density lipoprotein receptor (Basu et al., 19811, and accumulation of secretory products in the Golgi cisternae or in the cytoplasm (Oda and Ikehara, 1982). It has also been shown that monensin blocks Semliki forest virus or vesicular stomatitis virus penetration into cultured cells and processing of virus glycoproteins (Strous and Lodish, 1980;