Often, we find that what we’re looking for is closer to home than we think. Exciting research is one of those things that you will find in abundance at McMaster University. For instance, you may or may not know that Dr. André Bédard, from McMaster’s very own Department of Biology, utilizes a unique model, that of chicken embryo fibroblasts (CEFs), to study cell proliferation and transformation.
Interestingly, Dr. Bédard’s current research focusses primarily on the control mechanisms of cell survival. By analyzing CEF behaviour in limiting oxygen concentrations, known as hypoxia, it has been found that CEFs express the p20K lipocalin, a lipid-binding protein that has been confirmed to play a major role in the response mechanism to cell membrane-lipid damage (Erb et al., 2016[A]).
In order to characterize the role of p20K, experimental procedures involved the down-regulation of p20K, where results attributed a large portion of responsibility for membrane-lipid damage to lipid peroxidation, a mechanism of intense lipid degradation (Figure 1) (Erb et al., 2016[A]). In this process, free radicals steal electrons from lipids in cell membranes and generate highly unstable, reactive oxygen species (ROS), inducing immense cell damage (Barrera, 2012). As with all oxidative processes involving free radical reactions, lipid peroxidation also consists of three major steps: initiation, propagation, and termination (Figure 2).
Moreover, Dr. Bédard’s lab has established that p20K is essential for what has been termed the “Lipid Damage Response.” In this response, it is the expression of the p20K gene, for producing the p20K protein, that is required in the response program to membrane-lipid damage (Erb et al., 2016[A]). In the human body, hypoxic conditions can arise at the interior of proliferating cancer cells, where the absence of sufficient vasculature can lead to lack of oxygen availability (Eales, Hollinshead and Tennant, 2016). In addition, hypoxia is also prevalent in ischemia, a condition that involves the restriction of blood supply to tissues (Vishwakarma et al., 2017). Based on evidence indicating that a lack of p20K prevents the Lipid Damage Response and rather allows lipid peroxidation, it is imperative that further characterizing the mode of action of p20K can have clear implications in controlling cell survival in hypoxic conditions found in tumour and ischemic cells.
By observing the effects of the absence of p20K in cells, the critical role of p20K in alleviating lipid damage has become increasingly clearer. The demonstration involving p20K down-regulation implicates promising applications in the control of cell survival, where down-regulation would induce tumour cell death and up-regulation would lead to ischemic cell recovery. Dr. Bédard’s lab is one of many at McMaster University where research thrives and such applications become more and more tangible. In the big picture, it is worth noting that that which seems pervasive and distant––whether that is an opportunity, an achievement, or a solution to a problem––may be closer to home than we think.
References
Barrera, G., 2012. Oxidative Stress and Lipid Peroxidation Products in Cancer Progression and Therapy. International Scholarly Research Network (ISRN) Oncology, [e-journal] 2012. http://dx.doi.org/10.5402/2012/137289
Eales, K.L., Hollinshead, K.E.R. and Tennant, D.A., 2016. Hypoxia and metabolic adaptation of cancer cells. Oncogenesis, [e-journal] 5(1), pp.190–198. http://dx.doi.org/10.1038/oncsis.2015.50
Erb, M.J., Camacho, D., Xie, W., Maslikowski, B.M., Fielding, B., Ghosh, R., Poujade, F.-A., Athar, M., Assee, S., Mantella, L.-E. and Bédard, P.-A., 2016[A]. Extracellular Signal-Regulated Kinase 2 and CHOP Restrict the Expression of the Growth Arrest-Specific p20K Lipocalin Gene to G0. Molecular and Cellular Biology, [e-journal] 36(23), pp.2890–2902. http://dx.doi.org/10.1128/MCB.00338-16
Erb, M.J., Camacho, D., Xie, W., Maslikowski, B.M., Fielding, B., Ghosh, R., Poujade, F.-A., Athar, M., Assee, S., Mantella, L.-E. and Bédard, P.-A., 2016[B]. Figure 1: Large vesicle formation. Molecular and Cellular Biology, [e-journal] 36(23), pp.2890–2902. http://dx.doi.org/10.1128/MCB.00338-16
Vishwakarma, V.K., Upadhyay, P.K., Gupta, J.K. and Yadav, H.N., 2017. Pathophysiologic role of ischemia reperfusion injury: A review. Journal of Indian College of Cardiology, [e-journal] 7(3), pp.97–104. http://dx.doi.org/10.1016/j.jicc.2017.06.017
Young, I.S. and McEneny, J., 2001[A]. Figure 2: Lipid peroxidation mechanism. Biochemical Society Transactions, [e-journal] 29(2), pp.358–362. http://dx.doi.org/10.1042/bst0290358