Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Photodynamic therapy with the pro-drug 5-aminolaevulinic acid (ALA-PDT) is being used for the treatment of Barrett's oesophagus. We postulated that a first early course of ALA-PDT would increase protoporphyrin IX (PPIX) accumulation and thus the efficacy of a second course of ALA-PDT, by manipulating ferrochelatase (FC) and porphobilinogen deaminase (PBG-d) activity. Human EBV-transformed lymphoblastoid cells were used as a model of human tumour cells for the ability to form haem is present in all cells. After a single course of illumination (633 nm, 100 mW/cm2) the FC activity decreased significantly whereas the PBG-d activity did not change. During continued incubation with ALA following the first illumination, cells accumulated up to four times more PPIX than non-illuminated controls [220% +/- 30% versus (vs) 55% +/- 5%; p<0.001]. Two illuminations resulted in more cell death than one illumination (97% +/- 1% vs 80% +/- 2%; p<0.001). Since a second course of ALA-PDT within 3 hr after the first course resulted in a four fold increase in PPIX accumulation and significantly more cell death, we propose that a two course ALA-PDT scheme might improve the efficacy of this treatment for Barrett's oesophagus.
Cell Mol Biol (Noisy-le-grand) 2002 Dec
PMID:Two course illuminating scheme improves aminolevulinic acid photodynamic therapy in cell cultures. 1269 49

5-Aminolevulinic acid (ALA) and two of its esters were studied in cells in vitro and in vivo on skin of healthy hairless mice. In vitro, both esters, which are more lipophilic than ALA, induced higher PpIX fluorescence at lower concentrations compared with ALA. In vivo, ALA induced PpIX fluorescence more efficiently than the esters. The difference between ALA and the esters may be related to structures in the stratum corneum or to rate of penetration through this skin layer. The stratum corneum may bind the esters temporarily, and slow down their penetration into the living cells where PpIX is formed.
Cell Mol Biol (Noisy-le-grand) 2002 Dec
PMID:Production of protoporphyrin IX from 5-aminolevulinic acid and two of its esters in cells in vitro and tissues in vivo. 1269 50

5-Aminolevulinic acid (5-ALA) is a useful agent to enhance the detection of early epithelial lesions in head and neck cancers. It is applied either topically or systemically and converted intracellular into photosensitive protoporphyrin IX (PpIX). By ultraviolet light illumination malignant and fast proliferating lesions are detected by a characteristic red fluorescence and delineated by the bluish fluorescence of healthy tissue. To assess the elimination patterns 5-ALA, porphobilinogen (PBG) and porphyrin were measured 12h and 36h after administration in urine, 12h and 24h after examination in blood and in feces 12h after endoscopy. 5-ALA was applied either by inhalation (250 mg) or mouth rinse (200 mg). After both administration routes, excretion levels in urine returned to background levels within 12 hours after administration and only in feces values are slightly increased for PpIX and total porphyrin. Concentrations in erythrocytes were elevated, but not in plasma. No side effects were observed. According to our results the topical administration of 5-ALA is a useful method with satisfying fluorescence imaging results. Levels of metabolites in urine and plasma return to normal within 12 hours so that skin photosensitization can be neglected.
Res Commun Mol Pathol Pharmacol 2003
PMID:Excretion measurement of porphyrins and their precursors after topical administration of 5-aminolaevulinic acid for fluorescence endoscopy in head and neck cancer. 1568 9

Several drugs and stress are involved in the triggering of attacks in acute porphyrias. The central nervous system is extremely sensitive to free radical damage because of a relatively low antioxidant capacity. We have demonstrated that mice brain cholinergic system was altered by the effect of some porphyrinogenic agents. The aim of this work was to investigate how known porphyrinogenic drugs affect delta-Aminolevulinic acid synthetase (ALA-S), which is the response of heme oxygenase (HO) to this challenge and to evaluate if the xenobiotics studied develop stress oxidative in mice brain. HO activity was 50-70% induced after chronic Enflurane and Isoflurane anaesthesia, dietary Griseofulvin and starvation. An increase in mRNA HO expression was caused by chronic anaesthesia and Veronal treatments; instead allylisopropilacetamide (AIA) reduced mRNA expression. ALA-S activity was induced by acute administration of anaesthetics (89%), veronal (240%) and ethanol (80%), while ALA-S mRNA expression augmented by chronic administration of enflurane, AIA and veronal. Stress markers such as superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase activities and malondialdehyde and reduced glutathione levels showed different responses depending on the xenobiotic assayed. In conclusion, some of the drugs studied produced oxidative stress in brain that was confirmed through HO induction and this could be one of the factors leading to porphyric neuropathy.
Cell Mol Biol (Noisy-le-grand) 2005 Oct 03
PMID:Heme oxygenase, aminolevulinate acid synthetase and the antioxidant system in the brain of mice treated with porphyrinogenic drugs. 1630 71

Polyunsaturated free fatty acids (PUFAs) participate in normal functioning of the cell, particularly in control intracellular cell signalling. As nutritional components they compose a human diet with an indirect promoting influence on tumourogenesis. The PUFAs level depends on the functional state of the membrane. This work is focused on changes only of free unsaturated fatty acids amount (AA - arachidonic acid, LA - linoleic acid, ALA - alpha-linolenic acid, palmitoleic acid (PA) and oleic acid) in cell membranes of colorectal cancer of pT3 stage, G2 grade without metastasis. Qualitative and quantitative composition of free unsaturated fatty acids in the membrane was determined by high-performance liquid chromatography. It was shown that the malignant transformation was accompanied by a decrease in amount of LA and ALA while arachidonic and oleic acids increased. It is of interest that free AA levels are elevated in colon cancer, as AA is the precursor to biologically active eicosanoids.
Mol Cell Biochem 2007 Jan
PMID:Altered membrane free unsaturated fatty acid composition in human colorectal cancer tissue. 1685 11

A simple non-invasive ultra-violet/visible (UV/vis) diffusive reflectance spectroscopy combined with fiber-optics was investigated to elicit the dynamics of skin penetration in vivo of a pharmaceutical, aminolevulinic acid polyethylene glycol cream (5-ALA-PEG cream). Temporal data of the reflectance, R(lambda), were measured from a bare skin region and from a skin region treated with 5-ALA cream. The difference in apparent optical density [(DeltaAOD)=Deltalog[1/R(lambda)]] between the treated and untreated regions of the skin was gradually increased to a local maximum value with an increasing time of measurement, and then it was decreased in an oscillatory manner. This temporal increase in DeltaAOD was interpreted as a diminution of total reflectance by an increased scattering inside the skin tissue as topically applied materials penetrated gradually and temporally accumulated into the skin. A following decrease in DeltaAOD was attributed to diminished scattering effects as the penetrated materials gradually cleared out by cellular uptake of 5-ALA and circulation by epidermal capillary. In conclusion, it was possible to measure the skin absorption kinetics of the topically treated materials, including the penetration time and clearing out from the temporal course of the differential AOD.
Spectrochim Acta A Mol Biomol Spectrosc 2007 Mar
PMID:In vivo skin absorption dynamics of topically applied pharmaceuticals monitored by fiber-optic diffuse reflectance spectroscopy. 1687 71

Intracellular porphyrin generation following administration of 5-aminolaevulinic acid (5-ALA) has been widely used in photodynamic therapy. However, cellular uptake of 5-ALA is limited by its hydrophilicity, and improved means of delivery are therefore being sought. Highly branched polymeric drug carriers known as dendrimers present a promising new approach to drug delivery because they have a well-defined structure capable of incorporating a high drug payload. In this work, a dendrimer conjugate was investigated, which incorporated 18 aminolaevulinic acid residues attached via ester linkages to a multipodent aromatic core. The ability of the dendrimer to deliver and release 5-ALA intracellularly for metabolism to the photosensitizer, protoporphyrin IX, was studied in the transformed PAM 212 murine keratinocyte and A431 human epidermoid carcinoma cell lines. Up to an optimum concentration of 0.1 mmol/L, the dendrimer was significantly more efficient compared with 5-ALA for porphyrin synthesis. The intracellular porphyrin fluorescence levels showed good correlation with cellular phototoxicity following light exposure, together with minimal dark toxicity. Cellular uptake of the dendrimer occurs through endocytic routes predominantly via a macropinocytosis pathway. In conclusion, macromolecular dendritic derivatives are capable of delivering 5-ALA efficiently to cells for sustained porphyrin synthesis.
Mol Cancer Ther 2007 Mar
PMID:Macromolecular delivery of 5-aminolaevulinic acid for photodynamic therapy using dendrimer conjugates. 1736 82

Glutamyl-tRNA reductase (GluTR) is encoded by HEMA in higher plants and catalyzes in plastids the initial enzymatic step of tetrapyrrole biosynthesis eventually leading to heme and chlorophyll. GluTR activity is subjected to a complex regulation on multiple expression levels. An ethanol-inducible HEMA-RNA-interference (RNAi) gene construct was introduced into the tobacco genome to study the primary effects of low GluTR content on the tetrapyrrole biosynthetic pathway. During the first days of induced HEMA silencing the chlorophyll and heme contents were diminished in young leaves. HEMA mRNA and GluTR protein content were also strongly reduced. However, expression analyses revealed that none of the other tetrapyrrole biosynthesis genes were affected on the transcriptional level in a nine days period after HEMA inactivation. Previously generated transgenic tobacco lines with RNAi silenced expression of the glutamate 1-semialdehyde aminotransferase (GSA) gene did also not display changes of transcripts from selected genes of tetrapyrrole biosynthesis and photosynthesis. Although the transcript levels were not decreased after inactivation of HEMA and GSA-expression, enzyme activities for Mg chelatase and Fe chelatase were lower, which occurred in parallel to the loss of chlorophyll and heme content. Posttranslational modification of enzymes downstream of ALA-biosynthesis is proposed as a regulatory mechanism to adjust the flux through tetrapyrrole biosynthesis in balance to supply of ALA.
Plant Mol Biol 2007 Aug
PMID:HEMA RNAi silencing reveals a control mechanism of ALA biosynthesis on Mg chelatase and Fe chelatase. 1757 Dec 16

The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA, 22:6n-3) has been previously shown to facilitate some of the vital functions of astrocytes. Since some dietary oils contain alpha-linolenic acid (ALA, 18:3n-3), which is a precursor of DHA, we examined their effect on astrocyte development. Fatty acids (FAs) were isolated from commonly used oils and their compositions were determined by GLC. FAs from three oils, viz. coconut, mustard and linseed were studied for their effect on astrocyte morphology. Parallel studies were conducted with FAs from the same oils after heating for 72 h. Unlike coconut oil, FAs from mustard and linseed, both heated and raw, caused significant morphogenesis of astrocytes in culture. ss-AR binding was also substantially increased in astrocytes treated with FAs from raw mustard and linseed oils as compared to astrocytes grown in normal medium. The expression profile of the isoforms of GFAP showed that astrocyte maturation by FAs of mustard and linseed oil was associated with appearance of acidic variants of GFAP and disappearance of some neutral isoforms similar to that observed in cultures grown in serum containing medium or in the presence of DHA. Taken together, the study highlights the contribution of specific dietary oils in facilitating astrocyte development that can have potential impact on human health.
Cell Mol Neurobiol 2007 Dec
PMID:Effect of fatty acids isolated from edible oils like mustard, linseed or coconut on astrocytes maturation. 1782 64

MRC-5 fibroblasts infected with human cytomegalovirus (HCMV) reference strain AD 169 were treated with different concentrations of methylated alpha-lactalbumin (Met-ALA) or methylated beta-lactoglobulin (Met-BLG), as well as with their peptic hydrolysates, and with the highly basic polypeptides such as are L-polylysines (4-15 kDa). The antiviral activity was calculated by comparing the number of infected cells in the presence and absence of the tested substances. Both Met-ALA and Met-BLG, as well as their peptic hydrolysates, decreased the infectious activity of cytomegalovirus in fibroblast cells. As expected, L-polylysines showed the highest antiviral activity. However, the tested basic proteins and polypeptides despite their lower antiviral activities might be potentially quite useful in fight of arising drug resistance activities and the persistence capacities of this virus.
J Mol Microbiol Biotechnol 2007
PMID:Anticytomegaloviral activity of esterified milk proteins and L-polylysines. 1782 77


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