Disease relevance of Fdx1

• 1. Examination of adrenodoxin clones from a genomic DNA library in phage lambda revealed some clones bearing gene fragments interrupted by introns and other clones bearing processed pseudogenes [1].
• Ferredoxin (Fd), a small protein from Clostridium pasteurianum, has been selected for immunologic studies because of its limited number (two) of antigenic determinants [2].
• To establish a highly sensitive in vivo system, 1alpha-hydroxylase, adrenodoxin and NADPH-adrenodoxin reductase were coexpressed in E. coli cells [3].

High impact information on Fdx1

• Identification of an idiotypic marker of a major regulatory T cell of the immune response in B10.BR mice to ferredoxin. The relationship of idiotypic regulation to conventional hapten-carrier effects [4].
• Its active site structure and redox properties suggest that AIF functions as an electron transferase with a mechanism similar to that of the bacterial ferredoxin reductases, its closest evolutionary homologs [5].
• Assignment of the functional gene for human adrenodoxin to chromosome 11q13----qter and of adrenodoxin pseudogenes to chromosome 20cen----q13.1 [1].
• The T-cell line and T-cell clones derived from it release interleukin 2 not only in the presence of anti-Fd-B2 idiotype antibody but in the presence of ferredoxin [6].
• One of the proteins synthesized in the cytoplasm electrophoretically comigrates with purified beef adrenodoxin reductase and another with beef adrenodoxin [7].

Biological context of Fdx1

• Mouse adrenodoxin shows high amino acid sequence identity with other mammalian adrenodoxins and the four cysteines involved in the formation of the iron-sulfur cluster are present [8].
• A full-length cDNA encoding mouse adrenodoxin was isolated from a Y1 adrenocortical tumor cell lambda ZAP cDNA library [8].
• Southern blots of DNA from a panel of mouse/human somatic cell hybrids identified cross-hybridizing adrenodoxin DNA in two loci, chromosome 11q13----qter and chromosome 20cen----q13 [1].
• Fd11 TsF specifically and significantly diminished the secondary antibody response to Fd in DBA/2 mice [9].
• In both assay systems, the response has been shown to be H-2 linked: k, b, and s haplotypes respond to Fd, and H-2d mice are nonresponders [10].

Anatomical context of Fdx1

• Specificity of the Fd11 TsF for Fd was established by comparing it to another TsF isolated by us (A10 TsF) in a sandwich ELISA, and by demonstrating the specific reactivity to Fd of the hybridoma in calcium flux studies [9].
• Adrenocorticotropin acting through cyclic adenosine monophosphate (cAMP) regulates transcription of the bovine adrenodoxin (Adx) gene in the adrenal cortex [11].
• As a result, it was concluded that adrenodoxin requires both mitochondrial and cytosol ribosomal activities for its synthesis and integration into adrenal mitochondria [12].
• Delta2E1 was shown to be a soluble protein localized inside the mitochondria, displayed catalytic activity when reconstituted with adrenodoxin and adrenodoxin reductase, and was also present in mitochondria isolated from rat liver [13].
• The various ferredoxin preparations were tested for their ability to sensitize mice for use in the in vitro lymphocyte stimulation assay [14].

Associations of Fdx1 with chemical compounds

• Mouse cytochrome P-450 linked ferredoxin: its cDNA cloning and inducibility by dibutyryladenosine 3',5'-cyclic monophosphate and forskolin [15].
• Interaction between mitochondrial CYP27B1 and adrenodoxin: role of arginine 458 of mouse CYP27B1 [16].
• In Y-1 cells, 8Br-cAMP increased the abundance of all three proteins, while PMA/A23187 decreased the abundance of P450scc and Adx [17].
• Furthermore, the increase in steroid production induced by StAR-containing lysate was not observed when COS1 lysate containing high levels of another mitochondrially imported protein, adrenodoxin, was used [18].
• Other genes identified in this study as being induced in low iron and in the fur mutant include those encoding superoxide dismutase (sodA), fumarate dehydratase (fumC), bacterioferritin (bfr), bacterioferritin-associated ferredoxin (bfd), and multiple genes of unknown function [19].

Other interactions of Fdx1

• This differs from cholesterol side-chain cleavage cytochrome P450 and adrenodoxin, which are expressed continuously in most fetal adrenocortical cells from onset of expression at embryonic days 11-12 (E11-12) until term [20].
• Adrenodoxin and P450 reductase were detected in all regions, suggesting the presence of both mitochondrial and microsomal P450s throughout the brain [21].
• The ferredoxin promoter is relatively simple, consisting of a TATA box and two Sp1-binding sites [22].
• Immune response to ferredoxin; nonresponder status is not due to suppression [2].
• Under anaerobic conditions and with NADPH as a reducing agent, daunomycin is reduced in the presence of spinach ferredoxin: NADP+ oxidoreductase as the enzyme catalyst to its hydroquinone, from which intramolecular elimination of the C-7 glycoside proceeds to provide a quinone methide intermediate [23].

Analytical, diagnostic and therapeutic context of Fdx1

• Macrophage-derived NO. was detected by two independent methods: a bioassay for NO.-mediated relaxation of preconstricted rings of rabbit aorta; and a spectroscopic measurement of the reaction of NO. with clostridial ferredoxin, an Fe-S protein [24].
• The immune status of mice primed and boosted with Fd was assessed by using two parameters of immunity: T cell proliferation and serum antibody production with the ELISA method [10].
• By a fractionation/renaturation technique the Adx factor in mouse Y1 adrenocortical cells was found to be in the size range of 106-115 kDa by gel mobility shift assay [11].
• In previous studies, nine different lysine residues were identified by chemical and immunological cross-linking experiments as potentially interacting with Adx, while in the present study, two arginine residues have been identified from sequence alignments [25].
• Administration of the anti-idiotypic antibody (anti-Fd-B2) i.v. to B10.BR mice, or treatment of B10.BR T cell-enriched populations with anti-Fd-B2 + C prior to adoptive transfer to irradiated B10.BR recipients followed by challenge with Fd resulted in a significant increase in the production of anti-Fd antibodies [26].

References