The relative importance of environmental
hypoxia due to global climate change on organismal ability to adapt to chemical insult and/or mechanisms of these responses is not well understood. Therefore, we have studied the effects of combined exposure to
perfluorooctane sulfonamide (
PFOSA) and chemically induced
hypoxia on
membrane lipid profile and homeostasis. Primary salmon hepatocytes were exposed to
PFOSA at 0, 25 and 50 µM singly or in combination with either
cobalt chloride (CoCl2: 0 and 150 µM) or deferroxamine (DFO: 0 and 100 µM) for 24 and 48 h. CoCl2 and DFO were used to induce cellular hypoxia because these two chemicals have been commonly used in animal experiments for this purpose and have been shown to increase
hypoxia-inducible factor 1-alpha (HIF-1α) and
vascular endothelial growth factor (
VEGF) levels.
Fatty acid (FA) profiles were determined by GC-MS, while gene expression patterns were determined by quantitative PCR. Hypoxic condition was confirmed with time-related increases of HIF-1α
mRNA levels in CoCl2 and DFO exposed cells. In general, significant alterations of genes involved in
lipid homeostasis were predominantly observed after 48 h exposure. Gene expression analysis showed that
biological responses related to peroxisome proliferation (
peroxisome proliferator-activated receptors (PPARs) and
acyl coenzyme A (ACOX)) and FA desaturation (Δ5- and Δ6-desaturases: FAD5 and FAD6, respectively) and elongation (FAE) were elevated slightly by single exposure (i.e. either
PFOSA, CoCl2 or DFO exposure alone), and these responses were potentiated in combined exposure conditions. Principal component analysis (PCA) showed a clustering of peroxisome proliferation responses at transcript levels and FA desaturation against membrane FAs levels whose changes were explained by
PFOSA and chemically induced
hypoxia exposures. Overall, our data show that most of the observed responses were stronger in combined stressor exposure conditions, compared to individual stressor exposure. In general, our data show that
hypoxia may, singly or in combination with
PFOSA produce deleterious health, physiological and developmental consequences through the alteration of
membrane lipid profile in organisms.