Disease relevance of Dnahc8

• Homozygosity for the t haplotype allele of the testis-specifically expressed axonemal dynein heavy chain (axDHC) gene, Dnahc8, has been linked to male sterility resulting from aberrant sperm motility [1].
• The mouse t complex distorter/sterility candidate, Dnahc8, expresses a gamma-type axonemal dynein heavy chain isoform confined to the principal piece of the sperm tail [2].
• 5. Immunoelectron microscopy of infected macrophages and immunoblotting of isolated phagosomes showed that Mycobacterium vacuoles acquire the lysosomal membrane protein LAMP-1, but not the vesicular proton-adenosine triphosphatase (ATPase) responsible for phagosomal acidification [3].
• The mutant Brg1 protein is stable, assembles into SWI/SNF-related complexes, and exhibits normal ATPase activity but is unable to establish DNase I hypersensitivity sites characteristic of open chromatin [4].
• We show that transgenic expression of the gastric H/K ATPase beta subunit specifically prevents the onset of autoimmune gastritis after neonatal thymectomy [5].

Psychiatry related information on Dnahc8

• Our findings support in vitro evidence that glucocorticoid induced Na-K ATPase activity during critical periods of nephron development is an important regulatory point of this model [6].
• Here, expanding upon pilot gene expression studies, we have further analyzed the relationship between Na+/K+ ATPase and amyloid using APP+PS1 transgenic mice, a model that develops amyloid plaques and memory deficits in the absence of tangle formation and neuronal or synaptic loss [7].

High impact information on Dnahc8

• The murine La protein and the RNA binding subclass of calf thymus La protein showed ATPase/dATPase activity in the presence of DNA-RNA or RNA-RNA hybrids [8].
• Nitric oxide (NO) physiologically stimulates the sarco/endoplasmic reticulum calcium (Ca(2+)) ATPase (SERCA) to decrease intracellular Ca(2+) concentration and relax cardiac, skeletal and vascular smooth muscle [9].
• The most potent compounds inhibited the helicase, the primase and the DNA-dependent ATPase activities of the enzyme with IC50 (50% inhibitory concentration) values less than 100 nM [10].
• A complementary DNA encoding the entire alpha 1 subunit of the mouse Na+- and K+-dependent adenosine triphosphatase (ATPase) was inserted into the expression vector pSV2 [11].
• The ability to assay the biological activity of this ATPase in a transfection protocol permits the application of molecular genetic techniques to the analysis of structure-function relationships for the enzyme that establishes the internal Na+/K+ environment of most animal cells [11].

Chemical compound and disease context of Dnahc8

• Overexpression of wild-type p53 in M1 myeloid leukemia cells induces apoptotic cell death that was suppressed by the calcium ionophore A23187 and the calcium ATPase inhibitor thapsigargin (TG) [12].
• A Mg2+- and Ca2+-stimulated adenosine triphosphatase (ATPase) at the outer surface of intact Ehrlich ascites tumor cells is described [13].
• We found that c-Fos was degraded when WEHI7.2 mouse lymphoma cells were induced to undergo apoptosis with the calcium ATPase inhibitor, thapsigargin, or the glucocorticoid hormone, dexamethasone [14].
• Energy-dependent efflux of methotrexate in L1210 leukemia cells. Evidence for the role of an ATPase obtained with inside-out plasma membrane vesicles [15].
• The effects of 2,5-di(tert-butyl)-1,4-benzohydroquinone (tBHQ), a synthetic phenolic antioxidant and a blocker of the sarco-endoplasmic ATPase, were evaluated on low and high voltage-activated Ca(2+) currents (ICas) with rodent dorsal root ganglion, hippocampal, and motor neurons [16].

Biological context of Dnahc8

• Additional experiments demonstrate the existence of a testis-expressed mRNA with no significant open reading frame, a portion of which is antisense to the 5'-untranslated region of the highly divergent Dnahc8 isoform [1].
• This analysis shows that segmental exchange, either by gene conversion or double crossing-over, has occurred at molecular markers in the vicinity of a gene, Dnahc8, that is a candidate for the t complex distorter locus Tcd2 [17].
• A Brg1 mutation that uncouples ATPase activity from chromatin remodeling reveals an essential role for SWI/SNF-related complexes in beta-globin expression and erythroid development [4].
• To circumvent this early embryonic lethality, we performed an ENU mutagenesis screen and generated a Brg1 hypomorph mutation in the ATPase domain [4].
• Not only does this mutation establish a role for Brg1 during organogenesis, it also demonstrates that ATPase activity can be uncoupled from chromatin remodeling [4].

Anatomical context of Dnahc8

• The cumulative data imply that Dnahc8 may have acquired functional plasticity in the testis through the tightly controlled expression of both typical and unusual isoforms [1].
• We explored the roles of SWI/SNF-like BAF chromatin remodeling complexes in this process by progressive deletion of the ATPase subunit, Brg, through successive stages of early T cell development [18].
• The ATPase p97, a prototype of this superfamily, participates in organelle membrane fusion [19].
• Tape-stripping of murine abdominal wall skin achieved almost complete depletion of epidermal Langerhans cells within a few hours of application, as measured by cell surface ATPase and expression of Ia antigens [20].
• The characteristics of the interstitial dendritic cell found in heart were studied in detail, and this cell was shown to be negative for acid phosphatase, beta-glucuronidase, and ATPase activity, and certainly some and probably all of the cells were negative for nonspecific esterase activity [21].

Associations of Dnahc8 with chemical compounds

• Furthermore, incubation of Møs with sodium nitroprusside mimicked the L-arginine-dependent inhibition of H+ ATPase activity [22].
• In C57BL/1 mice analyses were done on ouabain-insensitive ATPase, 5'-nucleotidase, nonspecific esterase, and beta-glucuronidase, but no diet effects were seen [23].
• Loss of cell adenylates could not be explained by arrest of de novo purine synthesis or increased ATP consumption by the Na+-K+ ATPase or the mitochondrial F0-ATPase [24].
• To investigate the effects of proximal tubule NO on Na+/K(+)-ATPase, we induced NO production in mouse proximal tubule epithelial cells by treatment with lipopolysaccharide (LPS) and interferon-gamma (IFN gamma) followed by determinations of ouabain-sensitive ATPase activity [25].
• Despite the inability of the H(+)/K(+) ATPase to be endocytosed, the gastric acid secretory response to histamine or an antagonist was very similar to that of wild-type mice, indicating that control of H(+)/K(+) ATPase activity can occur independently of intracellular trafficking [26].

Physical interactions of Dnahc8

• Sarcolipin (SLN) inhibits the cardiac sarco(endo)plasmic reticulum Ca2+ ATPase (SERCA2a) by direct binding and is superinhibitory if it binds as a binary complex with phospholamban (PLN) [27].
• This finding rules out the possibility that contaminating F0 ATPase gives rise to the DCCD binding exhibited by PLP and confirms the possibility that PLP has proton channel activity, as suggested by Lin and Lees (1,2) [28].
• The high affinity for actin and the slow rate of ADP release helps the myosin head to remain attached to actin for a large fraction of each ATPase cycle and allows actin filaments to be moved by only a few myosin V molecules in vitro [29].

Regulatory relationships of Dnahc8

• PTH inhibited Na-K ATPase activity in cells expressing wild-type NHERF-1 associated with increased serine phosphorylation of the alpha subunit of the transporter [30].
• An important role for these cTnT sites is indicated by results demonstrating that ROCK-II induced a depression in tension and ATPase activity in skinned fiber bundles from a TG model in which cTnI is replaced by slow skeletal TnI, which lacks S23 and S24 and in which T144 is replaced by proline [31].
• We conclude that NO generated by mouse proximal tubule epithelial cell iNOS inhibits Na/K ATPase activity in an autocrine fashion and that this inhibition is accompanied by a reduction in Na-dependent solute transport [25].
• Residues 2-25 of phospholamban are insufficient to inhibit Ca2+ transport ATPase of cardiac sarcoplasmic reticulum [32].
• Sarco/endoplasmic reticulum Ca(2+) ATPase 2b was up-regulated to more rapidly remove Ca(2+) from the cytosol of RGS2(-/-) cells [33].

Other interactions of Dnahc8

• Here we report the complete physical isolation of the Ccua locus and the identification of a candidate gene for expression of both "whipless" and "curlicue" at its proximal end, an axonemal dynein heavy chain gene, Dnahc8, formerly mapped by interspecific backcross analysis near Pim1 [34].
• Our results argue that Dnahc8 is fundamental to flagellar organization and function in Domesticus, but not Spretus, and suggest that Dnahc8 is integral to both Hst6- and t-specific male infertility [34].
• The T complex distorter 2 candidate gene, Dnahc8, encodes at least two testis-specific axonemal dynein heavy chains that differ extensively at their amino and carboxyl termini [1].
• Regulation of cytoplasmic dynein ATPase by Lis1 [35].
• Wilson disease is an autosomal recessive disorder of hepatic copper metabolism caused by mutations in a gene encoding a copper-transporting P-type ATPase [36].

Analytical, diagnostic and therapeutic context of Dnahc8

• Cryoelectron microscopy and single-particle analysis revealed that a major conformational change of p97 during the ATPase cycle occurred upon nucleotide binding and not during hydrolysis as previously hypothesized [19].
• DNA-dependent ATPase (dATPase) and transcription activities copurify when delta is analyzed by hydrophobic interaction and ion-exchange HPLC, arguing that transcription factor delta possesses an ATPase (dATPase) activity [37].
• The cells were obtained by collagenase perfusion of the liver at an early stage of development of ATPase-deficient putative preneoplastic populations, and propagated from foci of epithelial cells which started growth in vitro [38].
• Column fractions containing 120-kDa protein as revealed by Western blot analysis also contain K+-EDTA ATPase activity [39].
• Immunocytochemistry was performed using antiserum against human intrinsic factor and H/K ATPase (a parietal cell marker), counting the percent of intrinsic factor-positive parietal cells [40].

References