Disease relevance of CYGB

• Neuroglobin and cytoglobin overexpression protects human SH-SY5Y neuroblastoma cells against oxidative stress-induced cell death [1].
• Its physiological role is unknown but, like hemoglobin, myoglobin, and cytoglobin/histoglobin, it may transport O(2), detoxify reactive oxygen species, or serve as a hypoxia sensor [2].
• These results indicate that STAP is a novel endogenous peroxidase catabolizing hydrogen peroxide and lipid hydroperoxides, both of which have been reported to trigger stellate cell activation and consequently promote progression of liver fibrosis [3].
• Reduction kinetics of hexacoordinate hemoglobins, including human neuroglobin and cytoglobin, and those from Synechocystis and rice, are compared to myoglobin, soybean leghemoglobin, and several relevant mutant proteins [4].
• Structurally homologous hexacoordinate hemoglobins (hxHbs) are also found in animals (neuroglobin and cytoglobin) and some cyanobacteria, where they are thought to play a role in free radical scavenging or ligand sensing [5].

Psychiatry related information on CYGB

• The authors report their experience on a workshop centered on brief psychotherapy (the STAPP model defined by Sifneos) in a postgraduate training in psychotherapy [6].
• Twenty patients were randomly assigned to either STAPP or a form of nondirective therapy almost devoid of psychodynamic elements but with common factors of psychotherapy intact [7].
• The primary measures used were the Family Environment Scale (R. H. Moos, 1981), the Parent Behavior Form (L. Worell & J. Worell, 1974), the revised Self-Monitoring Scale (M. Snyder, 1987), and the Texas Social Behavior Inventory (R. Helmreich, J. Stapp, & C. Ervin, 1974) [8].
• Although majority of the coefficient of variations were acceptable, about 23 (12.6%) participants showed abnormality in at least one parameter after analysis by the 'Peer Group Mean and SDI'. Using CLIA'88, 5 WBC (6.5%), 6 RBC (7.6%), 8 HGB (9.7%), 15 HCT (19.0%), and 7 PLT (8.0%) results were unsatisfactory [9].
• Eighty-one Shia Imami Nizari Ismaili Muslims living in Ontario, Canada, provided demographic data and completed the Bem Sex-Role Inventory (BSRI; Bem, 1981) and the Attitudes Toward Women Scale (AWS; Spence, Helmreich, & Stapp, 1973) [10].

High impact information on CYGB

• The CYGB promoter was shown by pyrosequencing to be significantly hypermethylated [2-fold increase of methylation index (MtI) in tumours] in 25/52 (48%) tumour samples compared with normal samples [11].
• Down-regulation of the cytoglobin gene, located on 17q25, in tylosis with oesophageal cancer (TOC): evidence for trans-allele repression [12].
• We now show that cytoglobin gene expression in oesophageal biopsies from tylotic patients is dramatically reduced by approximately 70% compared with normal oesophagus [12].
• Frequent genetic and epigenetic abnormalities contribute to the deregulation of cytoglobin in non-small cell lung cancer [11].
• Searching the human and mouse genome databases with the genes surrounding the pufferfish hemoglobin loci reveals that homologues of some of these genes are proximal to cytoglobin, a recently described novel member of the globin family [13].

Chemical compound and disease context of CYGB

• For the nine patients who received 5-FU at the recommended dose level the median low counts were WBC 3.5 (2.2-4.0), HGB 10.3 (9.0-12.3), and PLT (x 1000) 167 (133-280), and the incidence of any grade greater than or equal to 3 toxicity was 22% diarrhea, 17% tenesmus, and 22% frequent bowel movements [14].

Biological context of CYGB

• All these results indicate that CYGB gene expression can be up-regulated by c-Ets-1 and Sp1 motifs [15].
• In the crystal structure, ferric Cgb is dimerized through two intermolecular disulfide bonds between Cys38(B2) and Cys83(E9), and the dimerization interface is similar to that of lamprey Hb and Ngb [16].
• Cytoglobin is a novel candidate tumour suppressor gene highly methylated in upper aero-digestive tract squamous cancer [17].
• Characterization of human cytoglobin gene promoter region [15].
• This finding suggests that neuroglobin and cytoglobin protect SH-SY5Y cells against oxidative stress-induced cell death [1].

Anatomical context of CYGB

• In addition to the overexpression of ferritin and the iron accumulations assumed to result from the genetically incompetent ferritin molecule, additional contributions to the iron, heme, and hyaline deposits in this disease are sought with antibodies to 2 recently discovered globins in humans, neuroglobin and cytoglobin [18].
• Cytoglobin is predominantly expressed in fibroblasts and related cell types, but also in distinct nerve cell populations [19].
• The BC2 cell line derived from the human hepatocarcinoma, HGB, undergoes a spontaneous sharp differentiation process in culture as it becomes confluent, remains stably differentiated for several weeks, and may return to proliferation thereafter under appropriate density conditions [20].
• Blood samples were taken periodically from 30 workers and BLL, HGB (hemoglobin), RBC (red blood cells), WBC (white blood cells) and HCT (hematocrit) were measured [21].
• Human coronary endothelial cells were incubated with S-nitroso-N-acetyl-penicillamine (SNAP, an NO donor), oxyhemoglobin (HGB, an NO trapping agent), SNAP plus HGB, or inactive vehicle (control) [22].

Associations of CYGB with chemical compounds

• Structural characterization of the proximal and distal histidine environment of cytoglobin and neuroglobin [23].
• Picosecond time-resolved resonance Raman (ps-TR3) spectroscopy of transient five-coordinate heme species produced by the photolysis of carbon monoxide (CO) adducts of Cgb and Ngb showed Fe-His stretching (nu(Fe-His)) bands at 229 and 221 cm(-1), respectively [23].
• SH-SY5Y cells transfected with plasmid DNA containing the neuroglobin or cytoglobin sequence showed enhanced survival after exposure to 300muM H(2)O(2) for 24h as compared to untransfected controls [1].
• Both cysteine residues in cytoglobin, although localized in other positions than in human neuroglobin, may form a disulfide bond as well [24].
• The expression of STAP protein and mRNA was augmented time dependently in thioacetamide-induced fibrotic liver [3].

Other interactions of CYGB

• These structural characteristics of Cgb and Ngb are discussed in relation to their ligand binding and physiological properties [23].
• CYGB shares a common phylogenetic ancestry with vertebrate myoglobin from which it diverged by duplication before the appearance of jawed vertebrates [15].
• However, antibody-dependent cellular cytotoxicity (ADCC) mediated by human anti-CMV IgG (cytoglobin) as well as stimulation with low-dose interleukin-(IL)-2 or IL-15 enhanced lysis markedly [25].

Analytical, diagnostic and therapeutic context of CYGB

• Immunoelectron microscopy and proteome analysis detected STAP in stellate cells but not in other hepatic constituent cells [3].
• Among euvolemic patients who do not have ischemic heart disease, guidelines recommend a transfusion threshold of HGB levels in the range of 6.0 to 8.0 g/dL; patients who have HGB that is at least 10.0 g/dL are unlikely to benefit from blood transfusion [26].
• Before introduction of the proforma, junior medical staff were instructed in the procedure using specialised lumbar puncture manikins (Baby Stap; Laerdel, USA) [27].

References