The role of metallothioneins in the formation of hierarchical mechanisms of resistance to toxic compounds in young and old animals on the example of copper sulfate

Abstract

We used classical methods of biochemistry, chromolithography, atomic adsorption spectrometry for the determination of copper ions and MALDI-TOF mass spectrometry for the determination of metallothioneins. We have found sequential administration of small doses of copper sulfate provided the formation of resistance to subsequent lethal doses of copper sulfate. Age-dependent differences in the adaptive response match with the difference in the metallothioneins content in liver cells. In this case of adaptation formation, there was not only an increase in metallothioneins, but also a change in the intracellular distribution of copper ions. We revealed that a multiple increase in copper ions in mitochondria and endoplasmic reticulum of liver cells was accompanied by a slight decrease in the activity of antioxidant enzymes included in their composition. It has been suggested that metallothioneins are involved not only in the accumulation and retention of copper ions, but also in active inter-protein swap. Age-dependent differences in resistance, adaptability and long-term effects of copper ions are due to differences in the metabolic systems of copper metabolism before the toxic doses administration of copper sulfate, i.e. difference in initial states.