Metabolic Profiling of Hypoxic Cells Revealed a Catabolic Signature Required for Cell Survival

Hypoxia is one of the features of poorly vascularised areas of solid tumours but cancer cells can survive in these areas despite the low oxygen tension. The adaptation to hypoxia requires both biochemical and genetic responses that culminate in a metabolic rearrangement to counter-balance the decrease in energy supply from mitochondrial respiration. The understanding of metabolic adaptations under hypoxia could reveal novel pathways that, if targeted, would lead to specific death of hypoxic regions. In this study, we developed biochemical and metabolomic analyses to assess the effects of hypoxia on cellular metabolism of HCT116 cancer cell line. We utilized an oxygen fluorescent probe in anaerobic cuvettes to study oxygen consumption rates under hypoxic conditions without the need to re-oxygenate the cells and demonstrated that hypoxic cells can maintain active, though diminished, oxidative phosphorylation even at 1% oxygen. These results were further supported by in situ microscopy analysis of mitochondrial NADH oxidation under hypoxia. We then used metabolomic methodologies, utilizing liquid chromatography–mass spectrometry (LC-MS), to determine the metabolic profile of hypoxic cells. This approach revealed the importance of synchronized and regulated catabolism as a mechanism of adaptation to bioenergetic stress. We then confirmed the presence of autophagy under hypoxic conditions and demonstrated that the inhibition of this catabolic process dramatically reduced the ATP levels in hypoxic cells and stimulated hypoxia-induced cell death. These results suggest that under hypoxia, autophagy is required to support ATP production, in addition to glycolysis, and that the inhibition of autophagy might be used to selectively target hypoxic regions of tumours, the most notoriously resistant areas of solid tumours

Comparative effects of Facebook and conventional media on body image dissatisfaction

BACKGROUND: Appearance comparison has consistently been shown to engender body image dissatisfaction. To date, most studies have demonstrated this relationship between appearance comparison and body image dissatisfaction in the context of conventional media images depicting the thin-ideal. Social comparison theory posits that people are more likely to compare themselves to similar others. Since social media forums such as Facebook involve one’s peers, the current study aimed to determine whether the relationship between appearance comparison and body image dissatisfaction would be stronger for those exposed to social media images, compared to conventional media images. METHODS: A sample of 193 female first year university students were randomly allocated to view a series of either Facebook or conventional media thin-ideal images. Participants completed questionnaires assessing pre- and post- image exposure measures of thin-ideal internalisation, appearance comparison, self-esteem, Facebook use and eating disorder risk. RESULTS: Type of exposure was not found to moderate the relationship between appearance comparison and changes in body image dissatisfaction. When analysed according to exposure type, appearance comparison only significantly predicted body image dissatisfaction change for those exposed to Facebook, but not conventional media. Facebook use was found to predict higher baseline body image dissatisfaction and was associated with higher eating disorder risk. CONCLUSIONS: The findings suggest the importance of extending the body image dissatisfaction literature by taking into account emerging social media formats. It is recommended that interventions for body image dissatisfaction and eating disorders consider appearance comparison processes elicited by thin-ideal content on social media forums, such as Facebook, in addition to conventional media

Precursor mass prediction by clustering ionization products in LC-MS-based metabolomics

10.1007/s11306-013-0539-4Metabolomics961301-131