Cytochrome P450 20A1 in zebrafish: Cloning, regulation and potential involvement in hyperactivity disorders

Cytochrome P450 (CYP) enzymes for which there is no functional information are considered "orphan" CYPs. Previous studies showed that CYP20A1, an orphan, is expressed in human hippocampus and substantia nigra, and in zebrafish (Danio rerio) CYP20A1 maternal transcript occurs in eggs, suggesting involvement in brain and in early development. Moreover, hyperactivity is reported in humans with chromosome 2 microdeletions including CYP20A1. We examined CYP20A1 in zebrafish, including impacts of chemical exposure on expression. Zebrafish CYP20A1 cDNA was cloned, sequenced, and aligned with cloned human CYP20A1 and predicted vertebrate orthologs. CYP20A1s share a highly conserved N-terminal region and unusual sequences in the I-helix and the heme-binding CYP signature motifs. CYP20A1 mRNA expression was observed in adult zebrafish organs including the liver, heart, gonads, spleen and brain, as well as the eye and optic nerve. Putative binding sites in proximal promoter regions of CYP20A1s, and response of zebrafish CYP20A1 to selected nuclear and xenobiotic receptor agonists, point to up-regulation by agents involved in steroid hormone response, cholesterol and lipid metabolism. There also was a dose-dependent reduction of CYP20A1 expression in embryos exposed to environmentally relevant levels of methylmercury. Morpholino knockdown of CYP20A1 in developing zebrafish resulted in behavioral effects, including hyperactivity and a slowing of the optomotor response in larvae. The results suggest that altered expression of CYP20A1 might be part of a mechanism linking methylmercury exposure to neurobehavioral deficits. The expanded information on CYP20A1 brings us closer to "deorphanization" CYP20A1 functions and its roles in health and disease

Activation of Akt Is Essential for the Propagation of Mitochondrial Respiratory Stress Signaling and Activation of the Transcriptional Coactivator Heterogeneous Ribonucleoprotein A2

This article shows that mitochondrial respiratory dysfunction activates a stress signaling that induces Akt1 activation. Akt1 activation occurs through calcineurin-mediated IGF1R/PI3-K pathway. Akt1-mediated phosphorylation of hnRNPA2 is a key requirement for the propagation of stress signaling and activation of nuclear target genes

Blocking FSH induces thermogenic adipose tissue and reduces body fat

Functional Genomics of Systemic Disorder

Genetic diversity analysis and chemical profiling of Indian <i>Acorus calamus </i> accessions from South and North-East India

560-567Acorus calamus L. (Family: Acoraceae) is a well-known traditional, endangered, medicinal and aromatic plant mainly found in India and China. The plant is also widely used in industrial, pharmaceutical and food industries. In the present study, 20 different accessions of Indian A. calamus were subjected to the study of genetic diversity (RAPD), and cytogenetic and phytochemical (β-asarone) analysis. For RAPD analysis, 9 primers were chosen, which generated 107 DNA fragments. The average percentage of polymorphism was recorded to be 67.23%. The primer OPA 12 showed the highest (100%) polymorphism, whereas the lowest (38.2%) polymorphism was observed for the primer OPBB 6. The polymorphism information content (PIC) values ranged 0.44 (OPA 7) to 0.18 (OPA11), while marker index (MI) values ranged 4.74 (OPA 7) to 0.36 (OPA 11). A dendogram was constructed by UPGMA method and the robustness of the tree was confirmed by bootstrap analysis with 1000 pseudo samples. For cytogenetic analysis, the 20 A. calamus accessions were screened for their ploidy status. The accessions were found to be either diploid or triploids. The phytochemical analysis of β-asarone content was determined through by HPLC method. The β-asarone concentration varied in the range of 2.2 to 7.2 mg/100 mg. The results of present study indicated the presence of low level of polymorphism among the A. calamus accessions of South India and North-East India. The phytochemical and cytogenetic analysis revealed that both diploid and triploid have low concentration of β-asarone irrespective of their geographical location

Effect of latex concentration on epoxidation of natural rubber (NR) latex

Effect of latex concentration on the extent of epoxidation and physical properties of epoxidized natural rubber (ENR) was evaluated as a function of latex concentration in the range of 20-60% by weight. The epoxidation rate increased with increasing latex concentration. Physical properties and sequence distribution of an epoxy group of ENR with 30 mol % epoxy content was invariant with the latex concentration employed for epoxidation