Abstract
BackgroundRotenone inhibits the electron transfer from complex I to ubiquinone, in this way interfering with the electron transport chain in mitochondria. This chain of events induces increased levels of intracellular reactive oxygen species, which in turn can contribute to acceleration of telomere shortening and induction of DNA damage, ultimately resulting in aging. In this study, we investigated the effect of rotenone treatment in human fibroblast strains.ResultsFor the first time we here describe that rotenone treatment induced a hormetic effect in human fibroblast strains. We identified a number of genes which were commonly differentially regulated due to low dose rotenone treatment in fibroblasts independent of their cell origin. However, these genes were not among the most strongly differentially regulated genes in the fibroblast strains on treatment with rotenone. Thus, if there is a common hormesis regulation, it is superimposed by cell strain specific individual responses. We found the rotenone induced differential regulation of pathways common between the two fibroblast strains, being weaker than the pathways individually regulated in the single fibroblast cell strains. Furthermore, within the common pathways different genes were responsible for this different regulation. Thus, rotenone induced hormesis was related to a weak pathway signal, superimposed by a stronger individual cellular response, a situation as found for the differentially expressed genes.ConclusionWe found that the concept of hormesis also applies to in vitro aging of primary human fibroblasts. However, in depth analysis of the genes as well as the pathways differentially regulated due to rotenone treatment revealed cellular hormesis being related to weak signals which are superimposed by stronger individual cell-internal responses. This would explain that in general hormesis is a small effect. Our data indicate that the observed hormetic phenotype does not result from a specific strong well-defined gene or pathway regulation but from weak common cellular processes induced by low levels of reactive oxygen species. This conclusion also holds when comparing our results with those obtained for C. elegans in which the same low dose rotenone level induced a life span extending, thus hormetic effect.Electronic supplementary materialThe online version of this article (doi:10.1186/s12979-015-0038-8) contains supplementary material, which is available to authorized users.
Highlights
Oxidative stress is defined as an excessive load of Reactive Oxygen Species (ROS) which cause reversible or persistent damage on a cellular or systemic level
We investigated the effect of a low dose of rotenone as a stressor in three different primary human fibroblast cell strains: MRC-5 and WI-38 are from lung tissue while human foreskin fibroblasts (HFF) are skin derived
When treating young (PD 32) WI-38 fibroblasts with 0.1 μM rotenone, we detected no delay in senescence induction and no change in the replicative potential (Additional file 2: Figure S1A and B)
Summary
Oxidative stress is defined as an excessive load of Reactive Oxygen Species (ROS) which cause reversible or persistent damage on a cellular or systemic level. Oxidative stress is dose dependent [1]: high oxygen levels can cause severe damage while low levels of ROS can be beneficial to the organism, resulting in an extended life span [2, 3]. Such biphasic responses to a potentially harmful. Rotenone inhibits the electron transfer from complex I to ubiquinone, in this way interfering with the electron transport chain in mitochondria This chain of events induces increased levels of intracellular reactive oxygen species, which in turn can contribute to acceleration of telomere shortening and induction of DNA damage, resulting in aging. We investigated the effect of rotenone treatment in human fibroblast strains
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