Polyoxidovanadates [MoVIVV9O28]5- and [H2PtIVVV9O28]5- interact with CHO cell plasma membrane lipids causing aggregation and activation of a G protein-coupled receptor

Mono substituted heteropolyoxidovanadates, when compared to effects of a corresponding isopolyoxidovanadate (POV), were found to be more effective initiators of signal transduction by a G protein-coupled receptor (GPCR), specifically the luteinizing hormone receptor (LHR). Here we report that LHRs signal productively when CHO cells expressing the receptor are treated with two heteropolyoxidovanadates Pt IV in monoplatino(IV)nonavanadate(V) ([H 2 Pt VI V V 9 O 28 ] 5- , V 9 Pt), and Mo IV in monomolybdo(VI)nonavanadate(V) (Mo[ VI V V 9 O 28 ] 5- , V 9 Mo). Both substituted decavanadate derivatives were more effective than decavanadate which is more charged, has greater stability and forms the [V 10 O 28 ] 6- anion (V 10 ) in cell culture medium at pH 7.4. For viable CHO cells expressing 10 k or 32 k LHR/cell and treated with 11 μM V 9 Pt and 13 μM V 9 Mo, mono substituted heteropolyoxidovanadates significantly decreased the packing of plasma membrane lipids for about 1 h. This brief change in membrane structure was accompanied by increased aggregation of LHR and cell signaling as indicated by increased intracellular levels of cAMP. More pronounced changes in lipid packing and LHR signaling were associated with short acting heteropolyoxidovanadates than with the more stable V 10 . When LHR was overexpressed, V 9 Pt and V 9 Mo had little or no effect on membrane lipid packing or receptor aggregation and the LHR was constitutively activated as indicated by elevated intracellular cAMP levels. Speciation of V 9 Pt and V 9 Mo in H 2 O and cell medium was monitored using 51 V NMR spectroscopy and confirmed that V 9 Pt and V 9 Mo had greater effects on CHO cells despite decomposing more rapidly in the cell growth medium. Thus, under conditions that promote CHO cell growth, V 9 Pt and V 9 Mo, despite their smaller molecular charge and their reduced stability, favor LHR signaling over that induced by V 10 . Importantly, under the same experimental conditions, CHO cells treated with V 9 Pt and V 9 Mo do not exhibit as strong toxic effects observed for cells treated with the longer lived V 10 . In summary, unlike the longer lived V 10 which is more growth inhibitory to cells, monosubstituted heteropolyoxidovanadates are more effective in transiently initiating signaling by a G protein-coupled receptor but, because of rapid hydrolysis, inhibit cell growth less.