Nicotine affects protein complex rearrangement in Caenorhabditis elegans cells

Abstract

Nicotine may affect cell function by rearranging protein complexes. We aimed to determine nicotine-induced alterations of protein complexes in Caenorhabditis elegans cells, thereby revealing links between nicotine exposure and protein complex modulation. We compared the proteomic alterations induced by low and high nicotine concentrations (0.01 mM and 1 mM) with the control (no nicotine) in vivo by using mass spectrometry (MS)-based techniques, specifically the CTAB discontinuous gel electrophoresis coupled with liquid chromatography (LC-MS/MS and spectral counting. As a result, we identified dozens of C. elegans proteins that are present exclusively or in higher abundance in either nicotine-treated or untreated worms. Based on these results, we report a network that captures the key protein components of nicotine-induced protein complexes and speculate how the different protein modules relate to their distinct physiological roles. Using functional annotation of detected proteins, we hypothesize that the identified complexes can modulate the energy metabolism and level of oxidative stress. These proteins can also be involved in modulation of gene expression and may be crucial in Alzheimers disease. The findings reported in our study reveal intracellular interactions of many proteins with cytoskeleton and may contribute to the understanding of the mechanisms of nicotinic acetylcholine receptor (nAChR) signaling and trafficking in cells.\n\nSignificance of the studyMost of us are affected by nicotine, not only because of the common use of tobacco products. Nicotine is also included in many popular vegetables of the family Solanaceae, such as tomatoes and peppers. However, these two sources provide the body with radically different doses of nicotine.\n\nStrong biological effects of nicotine rely on binding to the nicotinic receptor, which partially mimics the action of the natural hormone acetylcholine. In our study we used the nematode Caenorhabditis elegans as a model organism. General principles of functioning of human cells and C. elegans cells are similar. The worm is, however, a compromise between simplicity and complexity, which may facilitate understanding of the more complex systems, like the human body. Our study revealed in the presence of a low nicotine concentration a different composition of polypeptides in the organism than in the presence of a high nicotine concentration. The rearrangements of protein complexes concern proteins involved e.g. in the course of Alzheimers disease, which seems interesting in the context of our aging societies. From the perspective of the development of biological research, the ability to identify the components of large protein complexes can contribute to a better understanding of the functioning of cells.