Non-toxic concentrations of verapamil (0.05 and 0.075 mM) and diltiazem (0.10 and 0.25 mM) sensitize CHO cells to heat killing at 44 degrees C. These drugs sensitize by reducing both the shoulder and the slope of the exponential survival curve. Exposure to verapamil or diltiazem in conjunction with the heat sensitizer procaine HCl at 44 degrees C reduced cell survival below that observed for procaine plus heat. The mechanism by which verapamil and diltiazem sensitize CHO cells to heat killing is not understood.
The potential of antibodies raised against insulin-like growth factor-1 (IGF-1) as a treatment to enhance the anabolic actions of IGF-1 has been demonstrated in both rodent and ruminant models. We investigated whether treatment of genetically normal rats with anti-IGF-1 immunoglobulin (Ig, raised in cattle) would enhance growth and if anti-IGF-1 Ig treatment would ameliorate live-weight loss in genetically normal rats offered a severely protein-restricted diet. Scatchard analysis was used to characterise ammonium sulphate precipitated bovine anti-IGF-1 Ig. Anti-IGF-1 Ig binding to 125 I-IGF-1 yielded an almost linear Scatchard plot, with a Hill co-efficient of 0.951 6 0.012, indicating a single class of IGF-1 binding sites. The affinity of anti-IGF-1 Ig for IGF-1 was 2.14 6 0.66 3 10 9 l/mol. The non-immune Ig preparation did not bind IGF-1. Rats were offered either a diet with a normal protein level (20%) or protein restricted (4% protein), and each dietary group was further treated with twice-daily i.p. injections of either diluent phosphate buffered saline, non-immune Ig or anti-IGF-1 Ig. Dietary protein level had a significant effect on live-weight gain, but there was no effect of non-immune Ig or anti-IGF-1 Ig on live-weight gain. Treatment with anti-IGF-1 Ig prevented the significant depression of cumulative dietary intake observed in diluent, and non-immune Ig treated groups offered the 4% protein diet. The cumulative dietary intake of the anti-IGF-1 Ig treated, 4% dietary protein group did not differ significantly from those of the groups offered the 20% protein diet. In addition, within the 4% dietary protein group, rats treated with non-immune Ig exhibited a cumulative feed intake that was intermediate between that of the diluent treated and anti-IGF-1 Ig treated groups (P , 0.05). Size exclusion chromatography was used to characterise in vitro 125 I-IGF-1 binding in end-point plasma from each treatment group. In comparison to control groups, anti-IGF-1 Ig treatment resulted in substantially increased 125 I-IGF-1 binding in the 30 to 40 kDa region and a concomitant reduction in elution of free 125 I-IGF-1. Protein restriction markedly depressed IGF-1 binding at ,150 kDa in the plasma of diluent and non-immune Ig treated groups. Anti-IGF-1 Ig treatment was effective in preventing this decrease in ,150 kDa binding. Thus, anti-IGF-1 Ig appears to have a beneficial effect on dietary intake in protein-restricted rats, which is associated with induced changes in IGF-1 binding profiles in plasma.
The ability of deuterium oxide (D2O) to protect a heat-sensitive and thermotolerance-impaired Chinese hamster ovary (CHO) mutant cell line, HS-36 (Harvey and Bedford 1988), from heat killing was examined and compared to the parent CHO 10B cell line (WT). Both non-thermotolerant (NT) and thermotolerant (TT) G1 populations were examined. D2O differentially protected the NT cell lines from heat killing, with thermal protection ratios (D0) of 2 x 5 and 4 x 3 for HS-36 and WT cells, respectively. D2O provided additional protection to TT cells, but now protected the TT HS-36 cells more than the TT WT cells when the thermal protection ratios of TT cells are compared with those of NT cells (1.15 versus 0.82). The differential protection from heat of the mutant and wild-type lines by D2O may be useful in studies of induced lesions in proteinaceous cellular systems (e.g. the nuclear matrix, cytoskeleton and plasma membrane) using these two paired cell lines.
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