Disease relevance of CYTB

• The X-linked form of chronic granulomatous disease (X-CGD) results from mutations in the gene encoding gp91phox, a 91-kD membrane glycoprotein that is the larger subunit of the respiratory burst oxidase cytochrome b [1].
• When stimulated in strictly anaerobic conditions with phorbol myristic acetate, macrophages activated in vivo by i.p. injection of Corynebacterium Parvum reduced approximately 40% of their total cytochrome b [2].

Psychiatry related information on CYTB

• The observation that chronic, but not acute treatment with imipramine and electroconvulsive shock produces a region-specific change in the levels of mRNA encoding cytochrome b suggests that this enzyme may be involved in the sequence of events resulting in an antidepressant action [3].

High impact information on CYTB

• Tumor necrosis factor-alpha increases the steady-state reduction of cytochrome b of the mitochondrial respiratory chain in metabolically inhibited L929 cells [4].
• We propose that the reduced cytochrome b promotes the formation of reactive oxygen species, lipid peroxidation of the cell membrane, and cell death [4].
• The apoprotein, a cytochrome b-like heme protein called pedin (molecular mass, 10,000 daltons) is itself not toxic, but the purified holoprotein is extremely toxic, causing anaphylaxis-like shock and death in experimental animals at low doses (LD50 70 micrograms/kg) [5].
• No correlation was found between capability to produce O2-) by different population of macrophages and their content of cytochrome b [2].
• In intact macrophages and neutrophils, Na-dithionite reduced greater than 75% of the cytochrome b measurable in disrupted cells [2].

Biological context of CYTB

• Molecular basis of macrophage activation. Expression of the low potential cytochrome b and its reduction upon cell stimulation in activated macrophages [2].
• The nucleotide sequences have been determined of the mitochondrial cytochrome b genes from a series of mouse cell mutants selected for increased inhibitor resistance [6].
• This region of cytochrome b is the most highly conserved during evolution and these inhibitor binding sites probably occur within the protein domain constituting the Qo reaction center [6].
• EXPERIMENTAL DESIGN: RNA and DNA were extracted from cultured C2C12 myotubes, blotted and probed with cDNAs specific for the mitochondrial gene products cytochrome b and cytochrome c oxidase I, nuclear-encoded sarcomeric troponin C, and cytoplasmic glyceraldehyde-3-phosphate dehydrogenase [7].
• In addition, cytb gene phylogenies (MP, ML, and BI) recovered R. fulvescens and R. hirsutus (ML and BI) as basal taxa within the subgenus Reithrodontomys [8].

Anatomical context of CYTB

• In resident peritoneal macrophages that produced five times lower amounts of O2-, cytochrome b reduction was instead undetectable [2].
• (3) The addition of gossypol to mitochondria respiring on pyruvate plus malate or succinate induces a more oxidized state of NAD+ and cytochrome b, respectively [9].
• Chronic antidepressant treatments increase cytochrome b mRNA levels in mouse cerebral cortex [3].
• In contrast to the increased mRNA levels of cytochrome b found in cortex, chronic treatment with these antidepressants did not alter mRNA levels in hippocampus, cerebellum, or liver [3].
• Mouse LA9 cell lines were selected for increased resistance to either HQNO or myxothiazol, inhibitors of electron transport which bind to the mitochondrial cytochrome b protein [10].

Associations of CYTB with chemical compounds

• Antimycin A, a mitochondrial respiratory chain complex III inhibitor that binds to cytochrome b, blocked the formation of reactive oxygen species, suggesting that the free radicals are generated at the level of cytochrome b [4].
• J774.16 cells produce O2- upon stimulation by PMA and aggregated IgG, but a variant clone derived from it, J774.C3C cells, do not, probably because of a functionally defective cytochrome b [11].
• Glycine-231 residue of the mouse mitochondrial protonmotive cytochrome b: mutation to aspartic acid deranges electron transport [12].
• (4) In pre-steady-state assays of cytochrome b reduction by quinol, the mutant shows a reduced extent of reduction [12].
• The mouse LA9 HQN-R11 cytochrome b mutant, in which the glycine residue at position 231 is replaced by aspartic acid, has increased resistance to all inhibitors of the Qn redox center [12].

Analytical, diagnostic and therapeutic context of CYTB

• When the proximity of the altered amino acid residues to the histidines involved in heme ligation is considered, the results support a model for cytochrome b folding in which there are eight transmembrane domains rather than the nine of the Widger-Saraste model [6].

References