Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.3 (phospholipase C)
 18,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Daily sc injection of gentamicin (100 mg/kg) for 4 days produced a significant decrease in the activities of renal cortical Na+,K+-ATPase and alkaline phosphatase. The observed reduction in renal functional enzymatic markers was associated with significant elevation in sphingomyelin, phosphatidylserine, phosphatidylglycerol, phosphatidylinositol, phosphatidylcholine, and total phospholipid. Gentamicin significantly decreased the activity of renal phospholipase C. Nitrendipine (25 mg/kg/day) for 7 days po for 4 days alone did not markedly alter the activities of kidney phospholipase C, alkaline phosphatase, and Na+,K+-ATPase or tissue phospholipid levels. Daily administration of nitrendipine for 3 days followed by concurrent treatment of nitrendipine and gentamicin failed to prevent antibiotic-induced renal histopathologic changes, phospholipidosis, or decrease in alkaline phosphatase. However, in rats simultaneously given nitrendipine and gentamicin the activity of Na+,K+-ATPase returned to control values, indicating a selective blocking action for nitrendipine. The inability of nitrendipine to prevent gentamicin-induced renal phospholipidosis or decreases in enzymatic function markers was associated with significantly elevated tissue aminoglycoside levels when compared to values seen in rats given only the antibiotic. Evidence suggests that nitrendipine is not effective in lowering the concentration of gentamicin in renal cortex. The effectiveness of an agent in providing protection against aminoglycoside nephrotoxicity may be associated with the ability of the drug to lower renal gentamicin content.
 ...
PMID:Inability of nitrendipine to protect against gentamicin nephrotoxicity in the rat. 255 58

Gentamicin inhibited phosphatidylinositol (PI) hydrolysis catalyzed by rabbit renal phospholipase C in a dose-dependent manner. The inhibition was potentiated by furosemide in a dose-dependent manner. Furosemide may enhance gentamicin nephrotoxicity by potentiating the inhibitory effect of gentamicin on brush-border membrane PI degradation.
 ...
PMID:Enhancement of gentamicin-induced inhibition of phosphatidylinositol hydrolysis in rabbit renal proximal tubular brush-border membrane by furosemide. 262 96

The effects of gentamicin on phospholipid levels and metabolism and the uptake of phosphatidylcholine (PC) adsorbed to low-density lipoprotein (LDL) were investigated in cultured human proximal tubular (PT) cells. Cells incubated with gentamicin (0.3 mM) for one to 21 days had a similar increase in the cell number and protein as compared to control cells. However, the cellular levels of phosphatidylcholine (PC) and sphingomyelin (SM), but not other phospholipids, increased in a time-dependent manner. Incubation of gentamicin (0.3 to 3.0 mM) resulted in a concentration-dependent increase in the cellular levels of PC (50% to 320%) and SM (20% to 40%). Gentamicin stimulated the incorporation of [14C]-acetate into diacylglycerol, PC, and SM in the order of 300%, 66%, and 20%, respectively, but not into lysophosphatidylcholine (LPC). Similarly, gentamicin stimulated the incorporation of [14C]-choline into PC and SM in the order of 300% and 172%, respectively, but not into LPC as compared to control cells. In addition, gentamicin also stimulated the incorporation of [14C]-choline into cytidine diphosphocholine (CDP-choline). However, the endocytosis of [14C]-PC-LDL was lower in cells incubated with gentamicin than in control cells. Thus, exogenously derived PC on LDL does not contribute to the increased cellular levels of PC in PT cells incubated with gentamicin. The activity of cytidine triphosphate (CTP):phosphocholine cytidyltransferase was moderately lower in cells incubated with gentamicin as compared to control. By contrast, the activity of phospholipase A1 and phospholipase C was twofold lower in cells incubated with gentamicin for 21 days as compared to control. Thus, increased incorporation of [14C]-acetate and [14C]-choline into PC in cells incubated with gentamicin may not only be due to increased endogenous synthesis but to decreased catabolism of newly synthesized PC. We conclude that gentamicin impairs the lysosomal catabolism of PC, leading to its accumulation in PT cells. This phenomenon may be an indication of gentamicin-induced nephrotoxicity in man.
 ...
PMID:Gentamicin-induced alterations in phospholipid metabolism in cultured human proximal tubular cells. 285 67

A simple and sensitive liposome immunoassay for gentamicin was developed using the cytolytic agent, phospholipase C, instead of complement. Liposomes entrapping a fluorescent marker, calcein, were prepared by the reverse-phase evaporation method from a mixture of dimyristoylphosphatidylcholine and cholesterol (molar ratio of 3:1). Gentamicin, a model analyte, was covalently coupled to phospholipase C by 1-ethyl-3-(3-dimethylamino-propyl)-carbodiimide and N-hydroxysuccinimide. Liposomes were lysed by gentamicin-phospholipase C conjugate and an entrapped fluorescent marker was released. The lytic activity of gentamicin-phospholipase C conjugate was inhibited in the presence of gentamicin antiserum. The standard calibration curve was constructed by plotting percentage of liposome lysis versus log concentration of free gentamicin. The standard calibration curve was linear over 2.5 pg/ml approximately 2.5 ng/ml of gentamicin concentrations. This newly developed immunoassay is simple, relatively rapid and potentially applicable to the determination of concentration of antigens, drugs and endogenous substances.
 ...
PMID:Liposome immunoassay (LIA) for gentamicin using phospholipase C. 815

Reperfusion of ischemic rat hearts initiates the generation of inositol(1,4,5)trisphosphate [Ins(1,4,5)P3] and arrhythmias, provided that either norepinephrine or thrombin is present. In the current study, effects on endothelin-1 (ET-1) responses were investigated. Reperfusion of catecholamine-depleted, [3H]inositol-labeled hearts in the presence of ET-1 caused an increase in [3H]inositol phosphates (7,073 +/- 1,004 to 17,300 +/- 206 counts.min-1.g tissue-1, means +/- SE, n = 4, P < 0.01), which was quantitatively greater than the release observed under normoxic conditions, but there was no increase in [3H]Ins(1,4,5)P3. Gentamicin (150 microM) inhibited inositol phosphate responses in the presence of either norepinephrine or thrombin but did not inhibit the response to ET-1, providing additional evidence that the inositol phosphate response to ET-1 does not involve formation of Ins(1,4,5)P3, even under reperfusion conditions. In contrast to norepinephrine and thrombin, ET-1 did not initiate reperfusion arrhythmias (4.4% ventricular fibrillation compared with 0% ventricular fibrillation in catecholamine-depleted controls). The data provide strong evidence that the effect of ischemia-reperfusion on inositol phosphate responses is specific for particular receptor types and eliminates G proteins, phospholipase C enzymes, and substrate availability as the primary factors responsible for Ins(1,4,5)P3 generation under reperfusion conditions.
 ...
PMID:Ins(1,4,5)P3 and arrhythmogenic responses during myocardial reperfusion: evidence for receptor specificity. 932 97

The in vitro postantibiotic effect (PAE) and the postantibiotic effect of subinhibitory concentrations (PA SME) of gentamicin were investigated on clinical isolates of Salmonella typhimurium, Salmonella enteritidis and Pseudomonas aeruginosa. The PAE was induced by 2 x MIC and 4 x MIC of gentamicin for 0.5 h. The PA SME were studied by the addition of 0.1, 0.2 and 0.3 x MIC during the postantibiotic phase of the bacteria. The S. enteritidis strain did no regrow after affecting of supra-subinhibitory concentrations for 24 h with exception of the concentration 2 x MIC + 0.1 x MIC. The PAEs against P. aeruginosa were nearly identical for all the suprainhibitory concentrations tested (4.4-4.6 h) and no regrowth after PA SME was observed. The studied pharmacodynamic parameters decreased the surface hydrophobicity of Salmonella sp., mainly of S. enteritidis, evaluated by the ability to bind Congo red and by the aggregation in solutions of ammonium sulphate (SAT). Gentamicin in suprainhibitory concentrations expressively decreased the phospholipase C production--an important virulence factor of P. aeruginosa.
 ...
PMID:Pharmacodynamic parameters of gentamicin and their effect on biological properties of gram-negative bacteria. 947 60

Gentamicin is well known to promote hair cell death in inner ear, but it also appears to activate opposing pathways that promote hair cell survival. In combination with others, our previous work has indicated that a K-Ras/Rac/JNK pathway is important for hair cell death and an H-Ras/Raf/MEK/Erk pathway is involved in promoting hair cell survival (Battaglia et al., Neuroscience 122(4):1025-1035, 2003). However, these data also suggested that a Ras-independent survival pathway for activation of MEK might be stimulated by gentamicin. To investigate alternatives to the Ras/Raf/MEK/Erk pathway in promoting hair cell survival, cochlear explants were exposed to gentamicin combined with several inhibitors of alternative pathways (LY294002, calphostin C, SH-6, U73122). When exposed to gentamicin with the PI3K inhibitor LY294002 (10, 50 microM), the protein kinase C (PKC) inhibitor calphostin C (50, 100 nM) or the PKB/Akt inhibitor SH-6 (5, 10 microM), hair cell damage was significantly increased compared to gentamicin alone. By Western blotting, strong PKB/Akt activation was observed in the organ of Corti following exposure to 50 microM gentamicin for 6 h. In addition, PKC activation by 12-O-tetradecanoylphorbol-13-acetate protected outer hair cells from gentamicin induced cell death. In contrast, the phospholipase C-gamma (PLCgamma) inhibitor U73122 (2, 5 microM) did not affect hair cell damage when combined with gentamicin. Also, phosphorylation of PLCgamma was not increased in the organ of Corti following gentamicin treatment, as evaluated by Western blot. The results indicate that PI3K promotes hair cell survival via its downstream targets, PKC and PKB/Akt. This suggests that both Ras-dependent and Ras-independent survival pathways are involved during gentamicin exposure. In contrast, PLCgamma activation of PKC does not appear to play a role.
 ...
PMID:A PI3K pathway mediates hair cell survival and opposes gentamicin toxicity in neonatal rat organ of Corti. 1705 65