Figure 4
CoA and P-PantSAc rescue phenotypes induced by HoPan in mice. (a) Mice were treated with HoPan, HoPan + CoA, or HoPan + P-PantSAc, and survival was determined. Survival curves are shown as Kaplan-Meier plots. Mice treated with HoPan alone had a median survival of 5 days, whereas mice treated with HoPan + CoA, HoPan + P-PantSAc survived till the end of the experiment at Day 11. (b) Liver samples from treated and untreated mice were isolated, and CoA levels were measured using mass spectrometry. (For 4b mean ± SEM is given). CoA measurements in liver derived from mice treated with standard diet, Pan-deprived diet alone, Pan-deprived diet + HoPan, Pan-deprived diet + HoPan + 100 mM CoA, Pan-deprived diet + HoPan + 300 mM CoA, Pan-deprived diet + HoPan + 100 mM P-PantSAc, and Pan-deprived diet + HoPan + 300 mM P-PantSAc were determined. (c) Mice were treated with indicated compounds and weight was measured daily. Mouse weight is given in grams and represented as means ± SEM (for P-PantSAc treated mice, n = 2 mice were used). (d) Food intake was determined and given in grams of food intake per animal. Results are presented as mean ± SEM of at least 3 animals per treatment (for P-PantSAc, n = 2 animals were used). (e) Liver levels of free carnitine and (f) long-chain acylcarnitines, expressed in pmol/mg protein, are shown as mean ± SEM. (for P-PantSAc, n = 2 animals were used). (g) Western blot analysis of tubulin acetylation in livers from mice treated with HoPan, HoPan + CoA, CoA, Hopan + P-PantSAc, P-PantSAc, and vehicle is shown. GAPDH was used as loading control. A representative blot of three independent experiments is shown. (h) Quantification of g. For all panels mean ± SEM is given, statistically significant differences were determined by Student t-test. *p < 0.05, **p < 0.01, ***p < 0.001.
