Rabbit Anti-Human SP1 polyclonal antibody

Identification of disease-causing genes that underlie complex traits, such as susceptibility to disease, is the primary goal of genetic and biomedical researches. Bovine mastitis is the most prevalent disease with substantial economic losses and animal welfare issues in dairy industry. Quantitative trait loci (QTLs) and single-nucleotide polymorphism or gene association data as biomarkers were used in the selection programs in this industry. In the current microarray-based study, the gene expression profiles of cows selected for high or low mastitis susceptibility affected by a specific QTL on Bos taurus autosome 18 (BTA18) with induced E. coli mastitis in acute phase (time point 24h) were used to perform functional genomics. The results of a functional enrichment analysis showed that the Q genotype (favorable allele) helps to correct suppression of the metabolic process during infection and help to moderate signaling pathways related to immune response and inflammation. The most important pathways suppressed by Q genotype are related to triggering the inflammatory and immune responses which cause moderate responses to infection. Furthermore, the pathways related to growth, cell proliferation and reproductive process enriched by down-regulated expressed genes. The results of network analysis showed that transcription factors TP53, SP1 ligands such as INS, IL1B, IFNG, TGFB1, EGF and protein kinase MAPK1 are the common regulatory factors in the constructed networks. These findings regardless of revealing the new biological process of gene regulatory network analysis of differentially expressed genes (DE)s in bovine mastitis, could also introduce the important key regulatory elements in resistance to mastitis.

DNA damage triggers cell death mechanisms contributing to neuronal loss and cognitive decline in neurological disorders, including traumatic brain injury (TBI), and as a side effect of chemotherapy. Mithramycin, which competitively targets chromatin-binding sites of specificity protein 1 (Sp1), was used to examine previously unexplored neuronal cell death regulatory mechanisms via rat primary neurons in vitro and after TBI in mice (males). In primary neurons exposed to DNA-damage-inducing chemotherapy drugs in vitro we showed that DNA breaks sequentially initiate DNA-damage responses, including phosphorylation of ATM, H(2)AX and tumor protein 53 (p53), transcriptional activation of pro-apoptotic BH3-only proteins, and mitochondrial outer membrane permeabilization (MOMP), activating caspase-dependent and caspase-independent intrinsic apoptosis. Mithramycin was highly neuroprotective in DNA-damage-dependent neuronal cell death, inhibiting chemotherapeutic-induced cell death cascades downstream of ATM and p53 phosphorylation/activation but upstream of p53-induced expression of pro-apoptotic molecules. Mithramycin reduced neuronal upregulation of BH3-only proteins and mitochondrial dysfunction, attenuated caspase-3/7 activation and caspase substrates' cleavage, and limited c-Jun activation. Chromatin immunoprecipitation indicated that mithramycin attenuates Sp1 binding to pro-apoptotic gene promoters without altering p53 binding suggesting it acts by removing cofactors required for p53 transactivation. In contrast, the DNA-damage-independent neuronal death models displayed caspase initiation in the absence of p53/BH3 activation and were not protected even when mithramycin reduced caspase activation. Interestingly, experimental TBI triggers a multiplicity of neuronal death mechanisms. Although markers of DNA-damage/p53-dependent intrinsic apoptosis are detected acutely in the injured cortex and are attenuated by mithramycin, these processes may play a reduced role in early neuronal death after TBI, as caspase-dependent mechanisms are repressed in mature neurons while other, mithramycin-resistant mechanisms are active. Our data suggest that Sp1 is required for p53-mediated transactivation of neuronal pro-apoptotic molecules and that mithramycin may attenuate neuronal cell death in conditions predominantly involving DNA-damage-induced p53-dependent intrinsic apoptosis.