Myc is involved in Genistein protecting against LPS-induced myocarditis in vitro through mediating MAPK/JNK signaling pathway.

BACKGROUND: Genistein is widely used as a pharmacological compound as well as a food additive. However, the pharmaceutical effects of Genistein on myocarditis and its potential mechanisms have not been studied in detail. METHODS: H9c2 cells were continuously stimulated by lipopolysaccharide (LPS) for 12 h to simulate the in vitro model of myocarditis injury. DrugBank, String, and GEO dataset were used to investigate specific genes that interacting with Genistein. KEGG and GO enrichment analysis were employed to explore Myc-related signaling pathways. Biological behaviors of H9c2 cells were observed with the support of cell counting kit-8, MTT and flow cytometry. Expression levels of cytokines including TNF-α and ILs were evaluated by enzyme-linked immunosorbent assay. Western blot was applied to detect the expression of Myc and MAPK pathway related proteins. RESULTS: Genistein alleviated the damage of H9c2 cells subjected to LPS from the perspective of elevating cells growth ability, and inhibiting cells apoptosis and inflammatory response. Through bioinformatics analysis, we identified Myc as the potential target of Genistein in myocarditis, and MAPK as the signaling pathway. Significantly, Myc was highly up-regulated in myocarditis samples. More importantly, by performing biological experiments, we discovered that Genistein relieved H9c2 cells apoptosis and inflammatory reaction which caused by LPS stimulation through inhibiting Myc expression. Additionally, the marked augmentation of p-P38 MAPK and p-JNK expression in LPS-induced cardiomyocyte model were blocked by Genistein and si-Myc. CONCLUSIONS: Our research revealed that Myc mediated the protective effects of Genistein on H9c2 cells damage caused by LPS partly through modulation of MAPK/JNK signaling pathway.

Decreased activities of lysosomal acid alpha-D-galactosidase A in the leukocytes of sporadic Parkinson's disease.

Parkinson's disease (PD) is a progressive neurodegenerative disease that affects aged people. Although a number of genes have been linked to familial PD, the genetic causes of sporadic PD that accounts for 90% of all PD cases remain unclear. Accumulating evidence has demonstrated that alpha-synuclein aggregation is essential to the pathogenesis of PD. Recent studies suggest that autophagic-lysosomal system play major roles in the process of alpha-synuclein aggregation. We hypothesized that lysosomal acid hydrolases may be involved in the alpha-synuclein degradation and aggregation. In this study, we examined the activities of 11 lysosomal acid hydrolases in peripheral blood leukocytes of 38 sporadic PD patients and 258 age- and sex-matched healthy controls. The activities of alpha-D-galactosidase A were significantly decreased in sporadic PD patients, compared to age- and sex-matched controls. In contrast, no significant differences of the activities of other 10 lysosomal acid hydrolases was observed. This initial study suggests that decreased activities of lysosomal alpha-D-galactosidase A in the central nervous system may be involved in the degradation and aggregation of alpha-synuclein protein and contribute to the pathogenesis of sporadic PD as a risk factor.