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

The activity of the Na(+)/K(+) ATPase was shown to be reduced during apoptosis and enhanced during cell proliferation. This work investigated whether TNF-alpha exerts also opposite effects on the Na(+)/K(+) ATPase in HepG2 cells and whether these effects are time-dependent. A time response study demonstrated that the activity and protein expression of the ATPase are decreased at 1h and increased at 4, 6 and 8h. This work focused on the up-regulatory 4h-response. TNF-alpha was shown to exert a stimulatory effect on cJNK and NF-kappaB and an inhibitory effect on caspases which, in the basal state, down-regulate the ATPase. The cytokine was found to target the caspases by activating JNK which in turn activates NF-kappaB. The activated transcription factor inhibits the caspases and frees the ATPase from their inhibitory action leading thus to its up-regulation.
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PMID:Signaling pathway underlying the up-regulatory effect of TNF-alpha on the Na(+)/K(+) ATPase in HepG2 cells. 2003 43

Acute exposure of acetaminophen (APAP), a widely used analgesic and antipyretic drug, causes severe renal damage and no specific agent has been reported so far that plays any beneficial role in this organ pathophysiology. In the present study, the protective role of taurine on APAP-induced nephrotoxicity was investigated in mice. In order to induce acute nephrotoxicity, APAP was administered at a single dose of 2g/kg body weight orally to male adult albino mice of Swiss strain. APAP exposure for 24h significantly increased plasma level of blood urea nitrogen (BUN), creatinine, uric acid, TNF-alpha, NO production, urinary gamma-glutamyl transpeptidase (gamma-GT) activity, total urinary protein and urinary glucose level accompanied by a decrease in Na(+)-K(+)-ATPase activity. Moreover, APAP administration significantly increased MDA, protein carbonylation, GSSG level, intracellular ROS production and cytochrome P450 enzyme (CYPP450) activity. The same exposure decreased GSH level, ferric reducing/antioxidant power (FRAP) as well as the activities of antioxidant enzymes indicating that APAP-induced renal damage was mediated through oxidative stress. Besides, APAP exposure significantly reduced mitochondrial membrane potential and induced up-regulation of CYP2E1 in renal tissues although JNK did not play any significant role in this APAP-induced renal pathophysiology. Caspase 9/3 immunoblot and DNA fragmentation analyses showed that APAP-induced renal cell damage was mostly necrotic in nature, although some apoptosis also occurred simultaneously. Taurine treatment both pre and post (150 mg/kg body weight for 3 days, orally) to APAP exposure, however, significantly reduced APAP-induced nephrotoxicity through its antioxidant properties, urinary excretion of APAP and suppression of CYP2E1. Results suggest that taurine might be a potential therapeutic candidate against APAP-induced acute nephrotoxicity.
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PMID:Taurine protects acetaminophen-induced oxidative damage in mice kidney through APAP urinary excretion and CYP2E1 inactivation. 2006 17

To elucidate the putative neuroprotective effects of ghrelin in subarachnoid hemorrhage (SAH)-induced brain injury, Wistar albino rats (n = 54) were divided into sham-operated control, saline-treated SAH, and ghrelin-treated (10 microg/kg/d IP) SAH groups. The rats were injected with blood (0.3 mL) into the cisterna magna to induce SAH, and were sacrificed 48 h after the neurological examination scores were recorded. In plasma samples, neuron-specific enolase (NSE), S-100beta protein, TNF-alpha, and IL-1beta levels were evaluated, while forebrain tissue samples were taken for the measurement of malondialdehyde (MDA), glutathione (GSH), reactive oxygen species levels, myeloperoxidase (MPO), Na(+)-K(+)-ATPase activity, and DNA fragmentation ratio. Brain tissue samples containing the basilar arteries were obtained for histological examination, while cerebrum and cerebellum were removed for the measurement of blood-brain barrier (BBB) permeability and brain water content. The neurological scores were impaired at 48 h after SAH induction, and SAH caused significant decreases in brain GSH content and Na(+)-K(+)-ATPase activity, and increases in chemiluminescence, MDA levels, and MPO activity. Compared with the control group, the protein levels of NSE, S-100beta, TNF-alpha, and IL-1beta in plasma were also increased, while ghrelin treatment prevented all SAH-induced alterations observed both biochemically and histopathologically. The results demonstrate that ghrelin alleviates SAH-induced oxidative brain damage, and exerts neuroprotection by maintaining a balance in oxidant-antioxidant status, by inhibiting proinflammatory mediators, and preventing the depletion of endogenous antioxidants evoked by SAH.
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PMID:The anti-inflammatory and neuroprotective effects of ghrelin in subarachnoid hemorrhage-induced oxidative brain damage in rats. 2020 13

TNF-alpha has recently been implicated in diabetic nephropathy, which is usually accompanied by higher sodium retention. The kidneys play a major role in sodium homeostasis by regulating tubular sodium reabsorption, a process geared by the sodium gradient established by the Na(+)/K(+) ATPase. The aim of this work was to investigate the effect of TNF on the ATPase, and consequently its implication in kidney malfunction, using LLC-PK1 cells. The cytokine reduced the Na(+)/K(+)ATPase activity significantly. In an attempt to elucidate the signalling pathway involved, PDTC (pyrrolidinedithiocarbamate), SP600125 and FK009 respectively inhibitors of NF-kappaB, c-JNK and caspases, were added to the cells in the presence and absence of TNF, and changes in the activities of JNK and PDTC were determined. The activity of the pump was assayed by measuring the ouabain-inhibitable release of inorganic phosphate. The effect of the cytokine was abrogated completely when JNK and caspases were inhibited but was unaffected by NF-kappaB inhibition. The role of each mediator in the signalling cascade was studied further by applying different combinations of the inhibitors. TNF-alpha was found to act at 1 h by activating caspases, which in turn activate JNK; the latter exerts an inhibitory effect on NF-kappaB, a transcription factor that stimulates the Na(+)/K(+) ATPase when active. It was concluded that TNF-alpha exerts opposite effects on the Na(+)/K(+)ATPase at different times, though the effects are always mediated via cJNK, NF-kappaB and caspases.
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PMID:TNF-alpha reduces the Na+/K+ ATPase activity in LLC-PK1 cells by activating caspases and JNK and inhibiting NF-kappaB. 2022 69

The small guanosine triphosphatase Rho and its target Rho kinase are involved in a heterogeneous spectrum of cellular activities, many of which are integral to cytoskeletal organization. Furthermore, the Rho kinases result in NF kappa beta activation and hence the induction of various pro-inflammatory cytokines including TNF-alpha, IL-1B and IL-6. ROCK2 is a downstream protein, whose expression is indicative of Rho Kinase activation. Given the diverse effects of Rho-kinase, including a potentially critical role in augmenting inflammation, ROCK2 expression was examined in biopsies of select autoimmune connective tissue diseases as compared to control diagnoses. Select cases of lupus erythematosus, dermatomyositis, autoimmune sclerodermoid disorders and Kohlmeier-Degos disease (a distinctive vasculopathy that occurs in the other aforesaid conditions but also as a forme fruste microvascular and arteriopathic syndrome) were studied. Control biopsies included normal skin and cutaneous inflammatory conditions unrelated to collagen vascular disease/autoimmune disease. We found ROCK2 expression significantly increased in biopsies of lupus erythematosus, dermatomyositis, scleroderma and Kohlmeier-Degos disease. A pattern emerged of consistent marked ROCK2 upregulation in endothelium and variable expression in inflammatory cells and epithelium. While expression was undetectable in normal skin, it was found in inflamed skin unrelated to specific autoimmune disease. The staining pattern could approach that seen in study group cases but was less pronounced and preferentially upregulated in the endothelium, with a lesser extent of staining in the epidermis and inflammatory cells. Rho kinase is a driving factor in diverse cutaneous diseases especially autoimmune disease and Kohlmeier-Degos disease. This significantly upregulated pathway defines a potential target for biologic therapy.
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PMID:Enhanced cutaneous Rock2 expression as a marker of Rho Kinase pathway activation in autoimmune disease and Kohlemeier-Degos disease. 3177 51


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