Disease relevance of ATP12A

• Vacuolar H+-ATPase B1 Subunit Mutations that Cause Inherited Distal Renal Tubular Acidosis Affect Proton Pump Assembly and Trafficking in Inner Medullary Collecting Duct Cells [1].
• ATP1AL1 mRNA was overexpressed in 12 out of 20 human colorectal adenocarcinomas compared with the level in the accompanying normal mucosa [2].
• Proton pump inhibitors in acute peptic ulcer bleeding [3].
• Proton-pump inhibitors or H2-receptor antagonists for Helicobacter pylori eradication-a meta-analysis [4].
• Proton pump inhibitor-therapy refractory gastro-oesophageal reflux disease patients, who are they [5]?

Psychiatry related information on ATP12A

• Proton-pump inhibitor treatment resulted in an absolute risk reduction of peptic ulcer by 36.6% in acute and 34.6% in chronic non-steroidal anti-inflammatory drugs/aspirin users; indeed, the number needed to treat to avoid one peptic ulcer in elderly non-steroidal anti-inflammatory drugs/aspirin users was three both in acute and chronic users [6].
• Proton pump inhibitor-based triple therapies have shown more consistent and higher eradication rates with a short duration of treatment, good patient compliance, fewer side effects, prompt symptom relief and fast ulcer healing [7].
• Once we have the correct diagnosis stabilized, life style modification should be the first step in the management of GERD, aided with antacids, H2 receptors antagonists and/or Proton pump inhibitors [8].

High impact information on ATP12A

• Proton-pump inhibition of gastric chloride secretion in congenital chloridorrhea [9].
• In this study we find that the intracellular Na+ content in cells expressing ATP1AL1 and gH,Kbeta is two times lower than that in control HEK 293 cells in response to incubation for 3 h in the presence of 1 microM ouabain [10].
• Proton pump activity is not measurable in the plasma membrane of unstimulated neutrophils but becomes readily detectable upon activation by soluble agonists [11].
• Proton pump inhibitors do not reduce atazanavir concentrations in HIV-infected patients treated with ritonavir-boosted atazanavir [12].
• Proton pump inhibitors are the mainstay of therapy for symptom relief, healing of erosive esophagitis, resolution of peptic ulceration, reduction of the risk for NSAID-induced mucosal damage, and prevention of disease recurrence [13].

Chemical compound and disease context of ATP12A

• Proton pump inhibitors (PPIs) [omeprazole, lansoprazole, pantoprazole, rabeprazole and esomeprazole] are widely utilised for the treatment of gastro-oesophageal reflux disease, as well as other acid-related disorders [14].
• BACKGROUND: Proton pump inhibitor triple therapy with clarithromycin and metronidazole has been widely used for Helicobacter pylori eradication [15].
• Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori [16].
• CONCLUSIONS: Proton-pump inhibitor therapy significantly reduced heartburn, but not other acetylsalicylic acid associated symptoms [17].
• OBJECTIVE: Proton pump inhibitors (PPI) and misoprostol decrease the risk of development of nonsteroidal antiinflammatory drug induced gastric ulcers and aid healing of upper gastrointestinal (GI) ulcers [18].

Biological context of ATP12A

• A fourth alpha gene of unknown function (alpha D) that was isolated by molecular cloning (ATP1AL1) was mapped to chromosome 13 [19].
• Stimulation of protein kinase C pathway mediates endocytosis of human nongastric H+-K+-ATPase, ATP1AL1 [20].
• All ATP1AL1 exons and 12 of its 22 introns were entirely sequenced [21].
• The family of human Na,K-ATPase genes. ATP1AL1 gene is transcriptionally competent and probably encodes the related ion transport ATPase [22].
• Human ATP1AL1 and corresponding genes of other mammals encode the catalytic alpha subunit of a non-gastric ouabain-sensitive H,K-ATPases, the ion pump presumably involved in maintenance of potassium homeostasis [23].

Anatomical context of ATP12A

• The human nongastric H+-K+-ATPase, ATP1AL1, shown to reabsorb K+ in exchange for H+ or Na+, is localized in the luminal plasma membrane of renal epithelial cells [20].
• Proton-pump-mediated acidification of lysosomes does not appear to be required for cystine transport in normal polymorphonuclear-leucocyte granular fractions, as reported for lymphoblast lysosomes [24].
• Proton pump gene expression is also upregulated in 3 independent cisplatin-resistant cell lines but not in vincristine- or etoposide-resistant cell lines [25].
• Proton pump inhibitors and gastric acid secretion [26].
• Similar to Na+-K+-ATPase, AL1/beta complexes are able to decrease intracellular Na+ concentrations in Na+-loaded oocytes, and their K+ transport depends on intra- and extracellular Na+ concentrations [27].

Associations of ATP12A with chemical compounds

• Genomic organization of the human ATP1AL1 gene encoding a ouabain-sensitive H,K-ATPase [21].
• Proton pump inhibitors (PPIs), drugs that are widely used for treatment of acid related diseases, are either substituted pyridylmethylsulfinyl benzimidazole or imidazopyridine derivatives [28].
• BACKGROUND: Proton pump inhibitors such as omeprazole and lansoprazole are mainly metabolized by CYP2C19 in the liver [29].
• BACKGROUND: Proton pump inhibitors such as omeprazole produce a long-lasting inhibition of gastric acid secretion associated with significant increases in plasma gastrin [30].
• Proton pump inhibitors play an important role in increasing the bioavailability of antibiotics in the gastric mucus by altering gastric volumes and increasing the stability of some antibiotics, e.g., clarithromycin [31].

Physical interactions of ATP12A

• CONCLUSIONS: Proton-pump inhibitors interact with and are metabolized by several human cytochromes P450, but only pantoprazole is also metabolized by a sulfotransferase [32].

Regulatory relationships of ATP12A

• BACKGROUND: Proton pump inhibiting drugs strongly decrease gastric acid secretion and have proven more effective in the treatment of reflux oesophagitis than H2-receptor antagonists [33].

Other interactions of ATP12A

• Eight expressed sequence tags, previously assigned to 13q11-q12 (D13S182E, D13S183E, D13S502E, D13S504E, D13S505E, D13S837E, TUBA2, ATP1AL1), were localized on the YAC contig [34].
• BACKGROUND: Proton-pump inhibitors, such as lansoprazole, are metabolized in the liver by CYP2C19 and cannot inhibit acid sufficiently in homozygous extensive metabolizers of CYP2C19 [35].
• Pairwise linkage analysis established linkage between ATRC1 and ATP1AL1, D13S1, D13S6, D13S10, D13S11, D13S21, D13S22, D13S33, D13S36, and D13S37 [36].
• BACKGROUND: Proton pump inhibitors are superior to H2-receptor antagonists in the prevention of relapse of oesophagitis, but few data directly compare the relative efficacies of lansoprazole and omeprazole in preventing oesophagitis relapse over a prolonged period [37].
• Proton pump inhibitor treatment of patients with gastroesophageal reflux-related chronic cough: a comparison between two different daily doses of lansoprazole [38].

Analytical, diagnostic and therapeutic context of ATP12A

• We constructed primers specific for ATP1AL1 and performed RT-PCR on RNA isolated from human placenta and human kidney [39].
• The ATP1AL1 protein was identified as a 114 kD band in both MVM and BM by Western blot, however, the protein was more abundant in the MVM [39].
• A series of Northern blot hybridization experiments using probes derived from the rat gastric H+,K(+)-ATPase cDNA and the human ATP1AL1 gene revealed the presence of a 4.3-kilobase mRNA in colon that seemed likely to encode the distal colon H+,K(+)-ATPase, the enzyme responsible for K+ absorption in mammalian colon [40].
• Stable interaction of ATP1AL1 with either the endogenous Na(+)-K(+)-ATPase beta-subunit or the gastric H(+)-K(+)-ATPase beta-subunit was tested by confocal immunofluorescence microscopy and surface biotinylation [41].
• CONCLUSIONS: Proton-pump inhibitor treatment for ulcer bleeding produces small, but potentially important, reductions in transfusion requirements and length of hospitalization [42].

References