Disease relevance of GJA8

• Cx50 expression was diminished in malignant pheochromocytomas [1].
• Mutations in GJA8 cause 3.3% of congenital cataracts in the population of India [2].
• These vectors employ the cis-acting element (CAE I) that directs the transcription of one of the most strongly expressed genes of cowpox virus [3].
• Two insertion vectors have been constructed; each is designed to allow cloned genes to be placed immediately downstream of a modified version of CAE I within a poxvirus genome [3].
• Sixty-eight patients with non-small cell lung cancer were treated in a prospectively randomized study with cyclophosphamide, doxorubicin (Adriamycin), and etoposide (VP16-213) with cisplatinum (CAE +/- P) [4].

Psychiatry related information on GJA8

• When somatic cell hybrid DNAs were restricted with Eco R1 and Southern blots hybridized with the human Cx50 DNA probe, the characteristic human restriction pattern was observed only when human chromosome 1 was present in the hybrid panel [5].
• Hyperventilation was the most common precipitating factor for CAE, and sleep deprivation was the most common one for JME and GMA [6].

High impact information on GJA8

• Loci for autosomal dominant "zonular pulverulent" cataract have been mapped to chromosomes 1q (CZP1) and 13q (CZP3) [7].
• A missense mutation in the human connexin50 gene (GJA8) underlies autosomal dominant "zonular pulverulent" cataract, on chromosome 1q [8].
• Sequence analysis of the entire protein-coding region of the GJA8 gene from the pedigree detected a C-->T transition in codon 88, which introduced a novel MnlI restriction-enzyme site that also cosegregated with the cataract [8].
• CZP1, a locus for autosomal dominant "zonular pulverulent" cataract, previously had been linked with the Duffy blood-group-antigen locus on chromosome 1q [8].
• To map the CZP1 locus we performed linkage analysis using microsatellite markers on two distantly related branches of the original Ev. pedigree, which now spans eight generations [8].

Chemical compound and disease context of GJA8

• N-alpha-Cocoyl-L-arginine ethyl ester, DL-pyroglutamic acid salt (CAE), exhibited a strong inactivating effect on hepatitis B surface antigen [9].
• CAE completely inactivated hepatitis B surface antigen at the lowest concentration compared with various compounds including about 500 amino acid derivatives, sodium hypochlorite, 2,4,4'-trichloro-2'-hydroxydiphenyl ether, and some detergents [9].
• Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients [10].

Biological context of GJA8

• RESULTS: Several single nucleotide polymorphisms in CRYG, CRYBB2, and GJA8 genes were observed [11].
• CONCLUSIONS: This study confirms the previous provisional assignment of MP70 to human chromosome 1 and regionally localizes the gene to 1q21 [12].
• These results suggest that the C-terminus of human Cx50 is involved in pHi sensitivity, but has little influence over single-channel conductance, voltage dependence, or gating kinetics [13].
• The DNA probe contained the entire MP70 coding region within a clone isolated from a human genomic DNA library [12].
• We used the dual whole-cell patch-clamp technique to investigate the macroscopic and single-channel properties of gap junctional channels formed by wild-type human Cx50 and a truncation mutant (Cx50A294stop) after transfection of N2A cells [13].

Anatomical context of GJA8

• Immunohistochemistry showed that Cx50 expression seemed to be the predominant form of Cx expressed in human chromaffin cells, whereas Cx43 immunoreactivity was the most prominent form found in the adrenal cortex [1].
• The blocking action of 2-APB did not substantially alter transjunctional voltage-dependent gating of Cx50 gap junction channels, and recordings from poorly coupled pairs of Cx50-transfected N2A cells indicated that 2-APB reduced gap junction channel open probability without changing the main state single-channel conductance [14].
• We have examined the effect of three lens fiber cell membrane proteins, MP20, MP26 and MP70, on the permeability properties of unilamellar phospholipid liposomes [15].
• There was no Cx50 expression observed and Cx40 was localized in the endothelial cells of blood vessels, with the Huntington's diseased brains having more numerous and smaller blood vessels than normal tissue [16].
• HeLa cell nuclear extract contained a protein that specifically binds to CAE1 and CAE2 and recognized by anti-ZNF143 antibody [17].

Associations of GJA8 with chemical compounds

• Mefloquine (MFQ) selectively blocks exogenously expressed gap junction channels composed of Cx50 but not Cx46 [18].
• For CAE and CAVE, the RDI of the regimens correlated positively with MS in extensive-stage disease as did the C RDI [19].
• An analysis of Alzheimer-affected hippocampal and control samples showed that the specific activity (in units per milligram of sodium dodecyl sulfate-soluble protein) of MP-70 varied less than the activities of MP-100 and MP-130 between the two groups [20].
• Although no treatment consensus exists, currently recommended regimens for SCLC include PE (cisplatin and etoposide), CAV (cyclophosphamide, doxorubicin, and vincristine), CAE (cyclophosphamide, doxorubicin, and etoposide), and CAVE (cyclophosphamide, doxorubicin, vincristine, and etoposide) [21].
• Twenty of the sera (i.e. 15%) contained antibodies which agglutinated sheep erythrocytes (SE) coated with a citric acid extract of skeletal muscle (CAE) [22].

Other interactions of GJA8

• Gap junction channels formed by connexin 50 (Cx50) are critical for maintenance of lens transparency [13].
• We show now that MP70 can be solubilized separately from MIP in mild detergent solutions, and that this treatment results in the dissociation of the fibre gap junctions [23].

Analytical, diagnostic and therapeutic context of GJA8

• METHODS: Fluorescence in situ hybridization (FISH) was used to regionally map the human MP70 gene [12].
• Solubilized MP70 was isolated as 16.9 S particles by velocity gradient centrifugation and in the electron microscope had the appearance of short double-membrane structures consistent with connexon-pairs [23].
• An immunofluorescence double-labeling study showed that Cx46 and Cx50 were labeled in the same gap junctions in both superficial and deeper cortical fibers of the normal lens [24].
• The median time to treatment failure was 22.9 wk for the CAE-P regimen and 15.0 wk for CAE (p = 0.032) [4].
• PATIENTS AND METHODS: Forty-six patients with extensive small-cell carcinoma of the lung were randomized to receive one of three Filgrastim schedules following cyclophosphamide, doxorubicin, and etoposide (CAE) chemotherapy for up to six cycles of treatment [25].

References