LSD1 negatively regulates autophagy in myoblast cells by driving PTEN degradation.

Lysine-specific demethylase 1 (LSD1) is a well characterized transcriptional regulator functioning on the chromatin to remove mono- and di-methyl groups from lysine 4 or lysine 9 of histone 3 (H3K4 or H3K9). LSD1 also has non-transcriptional activities via targeting non-histone substrates that participate in diverse biological processes. In this report, we determined that LSD1 negatively regulates autophagy in skeletal muscle cells by promoting PTEN degradation in a transcription-independent mechanism. In C2C12 cells, LSD1 inhibition or depletion significantly induced the initiation of autophagy; and autophagy resulted from LSD1 inhibition is associated with AKT/mTORC1 inactivation. Notably, the proteins of PTEN, a prominent repressive AKT modulator, are stabilized by LSD1 inhibition despite a decrease of its mRNA levels. Further data demonstrated that LSD1 interacts with PTEN protein and enhances its ubiquitination and degradation. Together, our findings identify a novel biological function of LSD1 in autophagy, mediated by regulating the stability of PTEN and the activity of AKT/mTORC1.

Antibody and cytokine responses to hydatid in experimentally infected Kazakh sheep with hydatidosis resistance haplotype.

Different MHC haplotype of Kazakh sheep has different resistance and susceptibility of hydatidosis. Notably, the MvaIbc-SacIIab-Hin1Iab haplotype of MHC-DRB1 exon two was associated with resistance hydatidosis. In order to analyze the antibody and cytokine responses to hydatidosis in Kazakh sheep with hydatidosis resistance haplotype, eight Kazakh sheep with the haplotype of MvaIbc-SacIIab-Hin1Iab were chosen as the test group, and other eight, which were not associated with hydatidosis resistance or susceptibility, were taken as control. After experimentally infected with hydatid orally, the blood was collected on 0, 7, 14, 30, 45, 60, 75, 90, 105, and 120 days. Serum and mRNA level of the cytokines IL-2, IFN-γ, TNF-α, IL-4, and IL-10 were evaluated by ELISA and fluorescence quantitative real-time polymerase chain reaction, respectively. The total white blood cells and leukomonocytes were determined by automation cytoanalyze. The level of IgE, IgG, and IgM were evaluated by ELISA. The results showed that the total white blood cells and leukomonocytes in test group were significantly higher than in control on 7, 45, 90, and 105 days post-infection (p.i.). The serum level of IL-2 in test group was significantly higher than in control on 45 days p.i., while the difference of IL-2 mRNA expression between test and control group was not significant. The serum level of TNF-α in test group was significantly higher than in control at 90 and 105 days p.i., and the TNF-α mRNA in test group was also significantly higher than in control on 90 days p.i. The level of IgE, IgG, and IgM in test group was higher than in control, but none was significant. The results suggested that the test group, which was predominant of Th1, could induce the protective immunity, while the control, which was predominant of Th2, could induce the susceptibility to infection of hydatidosis.