Authors: HIZLAN HINCAL AĞUŞ, SEDANUR YILMAZ, CANSIN OGEDAY ŞENGÖZ
Abstract: Camphor is widely used in pharmacy, the food industry, and cosmetics. In this study, we evaluate inhibitory and cytotoxic effects of camphor in the fission yeast (Schizosaccharomyces pombe), which presents a unicellular model in mechanistic toxicology and cell biology. Low-dose camphor exposure (0.4 mg/mL) activated autophagy, which was shown by GFP-Atg8 dots and transcriptional upregulation of Atg6 (Beclin-1 ortholog). Autophagy was also confirmed by using autophagy-deficient cells, which showed reduction in GFP-Atg8 dot formation. However, high-dose camphor exposure (0.8 mg/mL) caused dramatic cell death ratios, demonstrated by spot and colony-forming assays, even in autophagy-deficient cells. To unravel the underlying mechanism, this time, apoptosis-deficient cells were exposed to low- and high-dose camphor. Apoptosis was also confirmed by acridine orange/ethidium bromide staining. Among yeast apoptosis mediators, Aif1 was found to mediate camphor-induced cell death. In conclusion, differential regulation of autophagy and apoptosis, and switches between them, were found to be dose-dependent. The potential effects of camphor on autophagy and apoptotic cell death and underlying mechanisms were clarified in basic unicellular eukaryotic model, S. pombe.
Keywords: Camphor, autophagy, apoptosis, Atg8, Aif1, Schizosaccharomyces pombe
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