Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.1.3 (ATPase)
 65,361 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present studies were designed to examine the effects of ClC-2 ablation on cellular morphology, parietal cell abundance, H/K ATPase expression, parietal cell ultrastructure and acid secretion using WT and ClC-2-/- mouse stomachs. Cellular histology, morphology and proteins were examined using imaging techniques, electron microscopy and western blot. The effect of histamine on the pH of gastric contents was measured. Acid secretion was also measured using methods and secretagogues previously established to give maximal acid secretion and morphological change. Compared to WT, ClC-2-/- gastric mucosal histological organization appeared disrupted, including dilation of gastric glands, shortening of the gastric gland region and disorganization of all cell layers. Parietal cell numbers and H/K ATPase expression were significantly reduced by 34% (P<0.05) and 53% (P<0.001) respectively and cytoplasmic tubulovesicles appeared markedly reduced on electron microscopic evaluation without evidence of canalicular expansion. In WT parietal cells, ClC-2 was apparent in a similar cellular location as the H/K ATPase by immunofluorescence and appeared associated with tubulovesicles by immunogold electron microscopy. Histamine-stimulated [H+] of the gastric contents was significantly (P<0.025) lower by 9.4 fold (89%) in the ClC-2-/- mouse compared to WT. Histamine/carbachol stimulated gastric acid secretion was significantly reduced (range 84-95%, P<0.005) in ClC-2-/- compared to WT, while pepsinogen secretion was unaffected. Genetic ablation of ClC-2 resulted in reduced gastric gland region, reduced parietal cell number, reduced H/K ATPase, reduced tubulovesicles and reduced stimulated acid secretion.
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PMID:Genetic Ablation of the ClC-2 Cl- Channel Disrupts Mouse Gastric Parietal Cell Acid Secretion. 2637 82

Doxorubicin (DOX), an anthracycline-based antibiotic, is regularly used in the management of carcinomas, and haematological malignancies have been downplayed in chemotherapy because of its ability to induce dilated cardiomyopathy (DCM). Dexrazoxane is approved to combat the cardiotoxicity, but limited by its adverse effects. Redox imbalance and reactive oxygen species generation plays major role in DOX-induced cardiotoxicity. Histamine, known to mediate various cardiovascular effects, but nevertheless the role of histamine or its receptors in DOX-induced DCM is remained obscure. Hence, this study is aimed to examine the effect of Famotidine (FAM), a H2 receptor antagonist on DOX-induced DCM in Wistar rats. Myocardial antioxidant status, stress and apoptosis markers, myocardial morphology and function were evaluated as the end points. Treatment with FAM has alleviated DOX doxorubicin-induced cardiotoxicity by reducing oxidative and nitrosative stress evident from lipid peroxidation and total nitrate-to-nitrite ratio, and enhanced the activity of super oxide dismutase. Cardiac stress markers like LDH and Na+-K+ATPase activities as well as CK-MB and Cardiac troponin levels were reduced by FAM treatment. It also normalised the myocardial function as assessed by 2D echocardiography and myocardial index. Treatment imparted anti-apoptotic effect as evident from decrease in myocardial caspase 3 and 9 activity and cleaved PARP expression. Effect of FAM is found to be comparable to the standard ACE inhibitor Captopril (CAP). The results from this study collectively suggest H2 receptor antagonism as a novel therapeutic strategy to impart biochemical, structural and functional improvement indicating its cardio-protective activity.
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PMID:Histamine 2 receptor antagonism elicits protection against doxorubicin-induced cardiotoxicity in rodent model. 2888 71


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