Overlapping mechanism of the induction of genomic damage by insulin and adrenaline in human promyelocytic HL-60 cells

Abstract

Endogenous hormones systemically regulate the growth and metabolism and some prior studies have shown that their imbalance can have a potential to induce genomic damage in in vitro and animal models. Some conditions that are associated with elevated levels of endogenous hormones are hyperinsulinemia and intense exercise-induced stress causing increased adrenaline. In this study we test whether these two hormones, could cause an additive increase in genomic damage and whether they have an overlapping mechanism of action. For this, we use the human promyelocytic HL60 cells, as they express the receptors for both hormones. At doses taken from the saturation level of the individual dose response curves, no additivity in genomic damage was detected through micronucleus induction. This hints towards a common step in the pathway, which is under these conditions fully activated by each of the individual hormone. To investigate this further, individual and common parts in insulin and adrenaline signalling such as their respective hormone receptors, the downstream protein AKT and the involvement of mitochondria and NADPH oxidase (NOX) enzymes were studied. The results indicate no additive effect of high hormone concentrations in genomic damage in the in vitro model, which may be due to exhaustion of the NOX 2-mediated reactive oxygen production. It remains to be determined whether a similar situation may occur in in vivo situations.

Keywords: Adrenaline; HL60 cells; Insulin; Micronucleus test; NOX 2.