Mechanistic toxicity study of perfluorooctanoic acid in zebrafish suggests mitochondrial dysfunction to play a key role in PFOA toxicity

Effects of the PPARα agonist WY-14,643 on plasma lipids, enzymatic activities and mRNA expression of lipid metabolism genes in a marine flatfish, Scophthalmus maximus

“…Certainly, the timing of the injections did not provoke these differences in our work, since injections were done at day 0, 7 and 14, and sampling took place at day 7 and 21, each 7 days after the last injection. The mRNA and the protein level of both targets were included in this experiment, since it is well known that alterations of both levels do not always correlate (Hagenaars et al, 2013). Generally, the observed alterations of known targets of the fatty acid ␤-oxidation and the oxidative stress pathway in our study demonstrated that the exposure experiment was successful and that the higher concentration for injections of WY-14,643 (50 mg/kg) invoked a physiological response in turbot juveniles.…”

“…Effects of PPAR␣ agonists on the reduction of plasma lipids were confirmed in various freshwater fish species (Du et al, 2008;Prindiville et al, 2011;Velasco-Santamaria et al, 2011), and also led to increased VLDL phospholipids (Prindiville et al, 2011). Likewise, the peroxisome proliferator perfluorooctanoic acid increased the mRNA expression of apoeb in liver of male zebrafish and depleted liver energy stores (Hagenaars et al, 2013). A higher energy depletion resulting of exposure to the PPAR␣ agonist WY-14,643 is mirrored in the presented results on the reduction of plasma lipids (C-HDL, FC, NEFA), and may lead to a higher susceptibility to other environmental stressors.…”

“…Teleost fish are regarded as relatively insensitive to peroxisome proliferators and are for this reason often used as comparative model for humans (Tilton et al, 2008). Species-specific responses are described for fish exposed to fibrates, which show the involvement of a similar set of genes in the response (e.g., acox and cat), but not always the same effects (differences in species, male to female, mRNA to proteins, or time; e.g., zebrafish: (Hagenaars et al, 2013), salmon: (Arukwe and Mortensen, 2011). In our study, acox mRNA expression was significantly increased by hi-WY at day 7 (but not at day 21), and palmitoyl-CoA oxidase enzyme activity was significantly increased in hi-WY treatment compared to DMSO (but without group-specific differences at day 7 and 21).…”

Temperature-dependent effects of PFOS on risk recognition and fast-start performance in juvenile Spinibarbus sinensis

“…Given that exposure to PFCs (e.g. perfluorooctanoic acid) can result in an impairment of aerobic ATP production, depletion of liver glycogen stores and altered expression levels of transcripts involved in carbohydrate metabolism (Hagenaars et al 2013), we postulate that the reduced fast-start performance caused by chronic PFOS exposure was due to the disturbance of the Mauthner system and a constraint in muscle power output. According to Walker et al (2005), faster fast-starts increase the probability of evading predators.…”

Knockdown of Sucla2 decreases the viability of mouse spermatocytes by inducing apoptosis through injury of the mitochondrial function of cells

“…Most studies on Sucla2 focused on the mutation in the SUCLA2 nuclear gene and its relationship with the clinical syndromes of patients [1,3,6,26]. On the other hand, the majority of studies on the apoptosis of germ cells were focused on the detection of markers of mitochondrial dysfunction or apoptosis, such as ATP production, ROS level, Bcl2, or caspase 3/9 [8,18,35,36]. Our studies provide a new way of understanding the mechanism of mitochondrial dysfunction and the apoptosis of germ cells affected by mitochondrial proteins.…”