Anti-TOMM22 monoclonal antibody

Background: The aim was to research the molecular changes of bone cells induced by excessive dose of vitamin A, and analyze molecular mechanism underlying spontaneous fracture. Methods: The gene expression profile of GSE29859, including 4 cortical bone marrow samples with excessive doses of Vitamin A and 4 control cortical bone marrow samples, was obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DGEs) between cortical bone marrow samples and control samples were screened out and pathway enrichment analysis was undertaken. Based on the MSigDB database, the potential regulatory transcription factors (TFs) were identified. Results: A total of 373 DEGs including 342 up- and 31 down-regulated genes were identified. These DEGs were significantly enriched in pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism. Finally, the most significant regulatory TFs were obtained, including E2F Transcription Factor 1 (E2F1), GA Binding Protein Transcription Factor (GABP), Nuclear Factor, Erythroid 2-Like 2 (NRF2) and ELK1, Member of ETS Oncogene Family (ELK1). Conclusion: Key TFs including E2F1, GABP, NRF2 and ELK1 and their targets genes such as Ube2d3, Uba1, Phb2 and Tomm22 may play potential key roles in spontaneous fracture induced by hypervitaminosis A. The pathways of protein processing in endoplasmic reticulum, ubiquitin mediated proteolysis and glycerophospholipid metabolism may be key mechanisms involved in spontaneous fracture induced by hypervitaminosis A. Our findings will provide new insights for the target selection in clinical application to prevent spontaneous fracture induced by hypervitaminosis A. (C) 2017 Elsevier Ltd. All rights reserved.

Neurodegenerative disorders are dreadful diseases that affect millions of people worldwide. Mitochondrial dysfunction is closely associated with the development of neurodegenerative disorders. Phoenixin 20 is a newly discovered neuropeptide with a pleiotropic effect. This study showed that the presence of Phoenixin 20 promoted neuronal mitochondrial biogenesis in vitro. In cultured neuronal M17 cells, Phoenixin 20 increased the expression of mitochondrial regulators PGC-1 alpha, NRF-1, and TFAM at both mRNA and protein levels. The treatment of Phoenixin 20 increased the ratio of mitochondrial vs nuclear DNA (mtDNA/nDNA) and the multiple mitochondrial gene expression as revealed by increasing mRNA expression of Tomm22, Timm50, Atp5d, Ndufs3, and protein expression of NDUFB8. At a cellular level, Phoenixin 20 promoted mitochondrial respiratory rate and cellular ATP production. Mechanistically, we found that Phoenixin 20 induced the phosphorylation of CREB, which suggests that Phoenixin 20 promoted the activation of the CREB pathway. The blockage of CREB by its selective inhibitor H89 prevented the effect of Phoenixin 20 on mitochondrial regulators and biogenesis. Moreover, the study showed that Phoenixin 20 induced the expression of its tentative receptor GPR173 at the mRNA and protein level, and the silence of GPR173 in neuronal cells ablated all its effect on mitochondrial regulation. Collectively, we showed that Phoenixin 20 promoted neuronal mitochondrial biogenesis via the regulation of CREB-PGC-1 alpha pathway. This study revealed a new role and underlying mechanism of Phoenixin 20 in neuronal cells, suggesting it influences the therapeutic implication of neurodegenerative diseases.