Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As a contribution to the mechanisms of photochemotherapy, human skin homogenates were irradiated in the presence or absence of methoxsalen. The changes induced in LDH-, G-6-PDH-, GAPDH-, and GOT-activities were registered. Methoxsalen (50 mug/ml) failed to produce any significant effect. On pure G-6-PDH, methoxsalen exhibited a photoprotective action.
 ...
PMID:The mechanism of photochemotherapy. 95 27

All-trans retinoic acid and its derivative retinoid, two new compounds with expanding therapeutic spectrum in dermatology, were investigated in biochemical assays. Both substances provoke an increase in oxygen consumption of rat skin whereas in human skin only retinoid was found active in this respect. In resting yeast cells, both substances failed to exert any significant influence on oxygen consumption.--Pure G-6-PDH was inhibited by retinoic acid and retinoid in concentrations as low as 5 mug/ml. In human skin homogenates, LDH-, GAPDH-, and G-6-PDH-activities were inhibited by retinoic acid whereas GOT-, LAP-, and ALD-activites remained practically unchanged following an incubation with retinoic acid in concentrations between 1 and 100 mug/ml for 60 min.--The data collected in this study were briefly discussed with regard to the use of retinoic acid and its derivatives in psoriasis.
 ...
PMID:Influences of retinoic acid and retinoid on skin metabolism. Investigations of oxygen consumption and enzymatic activities of human skin. 98 76

Cyclooxygenase-2 (COX-2) expression in rat kidney is localized to the macula densa and the immediately proximal cTALH and increases after salt restriction. Either ACE inhibitors or AT1 receptor blockers increase COX-2 expression in both control and salt-restricted animals, suggesting that the RAS activation feedback inhibits renal cortical COX-2 expression. To determine whether increased COX-2 expression in response to ACE inhibition mediated increases in renin production, rats were treated with Captopril for 1 week with or without the specific COX-2 inhibitor, SC58236. Plasma renin activity increased significantly in the Captopril group. This increase was partially reversed by simultaneous treatment with SC58236. Kidney renin activity also increased in the Captopril group compared with control, which was also significantly inhibited by SC58236 treatment. Because of the localization of bNOS to MD and surrounding cTALH, the current study investigated the role of NO in the regulation of COX-2 expression. Rats were fed a normal diet, low salt diet or low salt diet combined with captopril and half of them were treated with the neuronal NOS inhibitor, 7-NI, and half with vehicle. After 7 days, mRNA was extracted and the microsome proteins purified from renal cortex. COX-2 mRNA expression was measured by Northern-blot and normalized with GAPDH. 7-NI treatment decreased COX-2 mRNA and immunoreactive COX-2 expression in each group. In summary, these studies indicate that COX-2 from macula densa/cTALH is a regulator of renin production and release. Angiotensin II may be a negative regulator of cTALH/macula densa COX-2 expression, and NO may mediate increased renal cortical COX-2 expression seen in volume depletion. These studies suggest important interactions between the NO and COX-2 systems in the regulation of arteriolar tone and the renin-angiotensin system by the macula densa.
 ...
PMID:Interactions of the renin-angiotensin system and neuronal nitric oxide synthase in regulation of cyclooxygenase-2 in the macula densa. 1069 79

Evidence implicates hyperglycemia-derived oxygen free radicals as mediators of diabetic complications. However, intervention studies with classic antioxidants, such as vitamin E, failed to demonstrate any beneficial effect. Recent studies demonstrate that a single hyperglycemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain seems to be the first and key event in the activation of all other pathways involved in the pathogenesis of diabetic complications. These include increased polyol pathway flux, increased advanced glycosylation end product formation, activation of protein kinase C, and increased hexosamine pathway flux. Superoxide overproduction is accompanied by increased nitric oxide generation, due to an endothelial NOS and inducible NOS uncoupled state, a phenomenon favoring the formation of the strong oxidant peroxynitrite, which in turn damages DNA. DNA damage is an obligatory stimulus for the activation of the nuclear enzyme poly(ADP-ribose) polymerase. Poly(ADP-ribose) polymerase activation in turn depletes the intracellular concentration of its substrate NAD(+), slowing the rate of glycolysis, electron transport, and ATP formation, and produces an ADP-ribosylation of the GAPDH. These processes result in acute endothelial dysfunction in diabetic blood vessels that, convincingly, also contributes to the development of diabetic complications. These new findings may explain why classic antioxidants, such as vitamin E, which work by scavenging already-formed toxic oxidation products, have failed to show beneficial effects on diabetic complications and may suggest new and attractive "causal" antioxidant therapy. New low-molecular mass compounds that act as SOD or catalase mimetics or L-propionyl-carnitine and lipoic acid, which work as intracellular superoxide scavengers, improving mitochondrial function and reducing DNA damage, may be good candidates for such a strategy, and preliminary studies support this hypothesis. This "causal" therapy would also be associated with other promising tools such as LY 333531, PJ34, and FP15, which block the protein kinase beta isoform, poly(ADP-ribose) polymerase, and peroxynitrite, respectively. While waiting for these focused tools, we may have other options: thiazolinediones, statins, ACE inhibitors, and angiotensin 1 inhibitors can reduce intracellular oxidative stress generation, and it has been suggested that many of their beneficial effects, even in diabetic patients, are due to this property.
 ...
PMID:New insights on oxidative stress and diabetic complications may lead to a "causal" antioxidant therapy. 1271 23

This study examines response of Anabaena sp. PCC 7120 to salt and UV-B stress by combining physiological, biochemical, proteomics and bioinformatics approaches. Sixty five significantly altered protein spots corresponding to 51 protein genes identified using MALDI-TOF MS/MS were divided into nine functional categories. Based on relative abundance, these proteins were grouped into four major sets. Of these, 27 and 5 proteins were up- and downregulated, respectively, both under salt and UV-B while 8 and 11 proteins showed accumulation in salt and UV-B applied singly. Some responses common to salt and UV-B included (i) enhanced expression of FeSOD, alr3090 and accumulation of MDA indicating oxidative stress, (ii) accumulation of PDH, G6P isomerase, FBPaldolase, TK, GAPDH and PGK suggesting enhanced glycolysis, (iii) upregulation of 6-PGD, 6PGL and NADPH levels signifying operation of pentose phosphate pathway, (iv) upregulation of Dps, NDK and alr3199 indicating DNA damage, and (v) accumulation of proteins of ribosome assembly, transcriptional and translational processing. In contrast, enhanced expression of RUBISCO, increased glycolate oxidase activity and ammonium content under salt signify the difference. Salt was found to be more damaging than UV-B probably due to a cumulative effect of ionic, osmotic and oxidative damage. A group of proteins having common expression represent decreased toxicity of salt and UV-B when applied in combination.
...
PMID:Salt and UV-B induced changes in Anabaena PCC 7120: physiological, proteomic and bioinformatic perspectives. 2411 24

Interpersonal differentiation between gasterozooids and gonozooids, inHydractinia echinata, is reflected by the pattern of extractable enzyme activities. With regard to their activity levels in the different hydranths the enzymes can be arranged in two groups. In the first group the specific activities are highest in gasterozooids and decline in the order gasterozooids>male gonozooids>female gonozooids. This group includes GAPDH, LDH, ICDH, and GPT. The activities of the second group are highest in female polyps and display the inverse sequence. This group comprises CS, GOT, and GLDH. When the GAPDH levels, taken as 100 pc each, are chosen as point of reference only this second sequence can be established and is now represented by MDH, ICDH, and G-6-PDH as well. 6-PGDH activity could not be determined in adult hydranths.According to the ratio of GAPDH/CS and the LDH level the gasterozooids prefer the anaerobic glycolytic pathway whereas in the sexual hydranths relatively more substrate is supplied at the disposal of the citrate cycle. Two metabolites of the citrate cycle, ketoglutarate and succinate, are known to promote the transformation of nutritive zooids into sexual zooids. The differences observed in the activities of GOT, GLDH, and ICDH, therefore, may be correlated not only with the production of gonocytes but also with the specific type of differentiation which in sexual hydranths is governed by a specific morphogen.
 ...
PMID:[Interpersonal differentiation of the enzymatic pattern in the polymorphic hydroidHydractinia echinata]. 2830 49

1. In order to elaborate some general correlations between metabolic pathways and morphogenetic events the activity-profiles of the enzymes GAPDH, LDH, CE, MDH, GOT, G-6-PDH, and 6-PGDH have been determined in different developmental stages. Unusually high activities of these enzymes could be extracted from unfertilized eggs. In the course of embryogenesis and metamorphosis two metabolic patterns alternate repeatedly. The first pattern is characterized by a relatively low glycolytic potency (low GAPDH- and LDH-levels) connected with a relatively high oxidative capacity (low ratio of GAPDH/CE and rising O2-consumption). This pattern, which indicates the predominance of energy production, is realized during cleavage and during the phase of contraction at the onset of metamorphosis. The second metabolic pattern combines high glycolytic potency (high GAPDH- and LDH-levels) with a high ratio of GAPDH/CE. This predominance of anaeroblic metabolism is correlated with high activities of MDH and GOT. An important portion of the substrate-flux may be directed towards anabolic processes. This metabolic condition is found during gastrulation and during the middle phase of metamorphosis: stages in which differentiation is initiated. This repeated change in the main metabolic behavior is also reflected by the operation of the pentose-phosphate-cycle. The activities of G-6-PDH and 6-PGDH decrease during cleavage and during early metamorphosis and increase during the differentiation of the planula and of the primary polyp. In the fully developed polyp, however, the 6-PGDH-activity disappears whilst that of the G-6-PDH remains high. 2. The induction of metamorphosis which normally is brought about by a bacterial agent and artificially by a Cs+-pulse, is characterized by an enhanced activity of the Na+\t-K+-ATPase. The maximum activity could be measured in homogenates and in living larvae 2 hrs and 0.5\2-1.5 hrs respectively after the application of Cs+. This finding supports the hypothesis that cation carriers are involved in the larval response to inductive stimuli. The induced peak of activity, in early metamorphosis, is followed by a second peak occurring spontaneously 3-4 hrs later. Relatively high ouabain-sensitive as well as ouabaininsensitive ATPase activities could also be observed in homogenates of young embryos.
 ...
PMID:[Activities of enzymes of carbohydrate-metabolism and of Na+-K+-ATPase durign Embryogenesis and Metamorphosis ofHydractinia echinata (Hydrozoa)]. 2830 96

Notwithstanding the numerous drugs available for liver cancer, emerging evidence suggests that chemotherapeutic resistance is a significant issue. HGF and its receptor MET play critical roles in liver carcinogenesis and metastasis, mainly dependent on the activity of receptor tyrosine kinase. However, for unknown reasons, all HGF-MET kinase activity-targeted drugs have failed or have been suspended in clinical trials thus far. Macroautophagy/autophagy is a protective 'self-eating' process for resisting metabolic stress by recycling obsolete components, whereas the impact of autophagy-mediated reprogrammed metabolism on therapeutic resistance is largely unclear, especially in liver cancer. In the present study, we first observed that HGF stimulus facilitated the Warburg effect and glutaminolysis to promote biogenesis in multiple liver cancer cells. We then identified the pyruvate dehydrogenase complex (PDHC) and GLS/GLS1 as crucial substrates of HGF-activated MET kinase; MET-mediated phosphorylation inhibits PDHC activity but activates GLS to promote cancer cell metabolism and biogenesis. We further found that the key residues of kinase activity in MET (Y1234/1235) also constitute a conserved LC3-interacting region motif (Y1234-Y1235-x-V1237). Therefore, on inhibiting HGF-mediated MET kinase activation, Y1234/1235-dephosphorylated MET induced autophagy to maintain biogenesis for cancer cell survival. Moreover, we verified that Y1234/1235-dephosphorylated MET correlated with autophagy in clinical liver cancer. Finally, a combination of MET inhibitor and autophagy suppressor significantly improved the therapeutic efficiency of liver cancer in vitro and in mice. Together, our findings reveal an HGF-MET axis-coordinated functional interaction between tyrosine kinase signaling and autophagy, and establish a MET-autophagy double-targeted strategy to overcome chemotherapeutic resistance in liver cancer. Abbreviations: ALDO: aldolase, fructose-bisphosphate; CQ: chloroquine; DLAT/PDCE2: dihydrolipoamide S-acetyltransferase; EMT: epithelial-mesenchymal transition; ENO: enolase; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GLS/GLS1: glutaminase; GLUL/GS: glutamine-ammonia ligase; GPI/PGI: glucose-6-phosphate isomerase; HCC: hepatocellular carcinoma; HGF: hepatocyte growth factor; HK: hexokinase; LDH: lactate dehydrogenase; LIHC: liver hepatocellular carcinoma; LIR: LC3-interacting region; PDH: pyruvate dehydrogenase; PDHA1: pyruvate dehydrogenase E1 alpha 1 subunit; PDHX: pyruvate dehydrogenase complex component X; PFK: phosphofructokinase; PK: pyruvate kinase; RTK: receptor tyrosine kinase; TCGA: The Cancer Genome Atlas.
 ...
PMID:The HGF-MET axis coordinates liver cancer metabolism and autophagy for chemotherapeutic resistance. 3078 11