Excited States of 8Be From the 7Li(d,n)8Be Reaction

Spear, RH

doi:10.1071/ph580502

Cited by 10 publications

(3 citation statements)

References 3 publications

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“…Thus, it is not certain that at a ratio of unity of Fe3+/Fe 2+ (where all Fe, regardless of its chelation status, is taken into account), the concentrations of the Fe 2÷ and Fe 3÷ which may actually act as reactive intermediates, are equal as well. LPO rates depend also on the metal chelation properties of thiols (19). This, and the work presented here support the hypothesis that Fe 2+ may be complexed to ligands other than the chelators used, perhaps a thiol.…”

Section: Vol 40 No 6 1996supporting

confidence: 84%

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The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

1996

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A T-glutamyl transpeptidase-glutathione (GGT-GSH) system induces transition metaldependent lipid peroxidation (LPO). The role of the transition metals iron and copper in this system was studied by determination of LPO rates, the rates of Fe 3+ reduction, and the steady state concentration of Fe 2÷ as function of concentration of o-phenanthroline or citrate. Optimum curves were obtained,compatible with the idea that Fe 2+ chelated by an entity other than o-phenanthroline or citrate is important in thioi-driven LPO. Cu enhanced LPO at low concentrations, inhibited LPO at high ones, and catalytically elevated the steady state concentration of Fe 2+. Relating the steady states of Fe 2+ at various chelator concentrations with those of LPO rates, indicate that a Fe2÷-O-O-Fe3+ complex may not be the principal oxidizing entity. The above, and the resistance of LPO to catalase, superoxide dismutase and mannitol are compatible with the notion that the Fe which participates in redox cycles is chelated to an entity that may be refractory to the action of these antioxidants. BIOCHEMISTRY and MOLECULAR BIOLOGY INTERNATIONALGSH-GGT-mediated LPO rates in rat liver microsomes, and the levels of the reduction of Fe 3÷, indicate that a complex other than Fe 2+-O-O-Fe a+ (perhaps thiol-Fe) complex is important for the induction of LPO by thiols, and that Cu enhances LPO by increasing the steady state of ferrous iron.MATERIALS AND METHODS Materials. Glutathione (GSH), dithiothreitol (DTY), glycylglycine, thiobarbituric acid (TBA), acivicin, butylated hydroxyanisol (BHA), catarase (CAT, 11,000 U/mg) and superoxide dismutase (SOD, 2,670 U/rag) were from Sigma, Saint Louis. o-phenanthroline (OP) was from Aldrich, Milwaukee. Malondialdehyde-bis-dimethylacetal was from Eastman-Kodak, Rochester. Cysteinyl-bisglycine was from Bachem, Torrance, CA. Rat liver and kidney microsomes were prepared from Wistar rats weighing 250 g. Organs were homogenized in 5 ml/g tissue of ice cold 50 mM sodium phosphate, 150 mM NaC! buffer pH 7.4 and were centrifuged at 9,000 x g for 20 min. The upper lipid layer was removed with filter paper, and the supernatant was centrifuged at 43,000 x g for 30 min, and the pellets (microsomes) were washed twice and resuspended in the same buffer, aliquoted, frozen and stored at -80°C. GGT activity was assayed with 1 ram L-3,-glutamyl-p-nitroanilide and 20 raM glycylglycine in 50 mM HEPES buffer pH 7.4 at 25°C. GGT activity was not affected by iron, copper, BHA, mannitol, OP, citrate or antioxidant enzymes at the concentrations used here. Protein concentration was determined with the Bradford reagent (Bio-Rad) with bovine serum albumin as a standard. The specific activities of GGT in liver and kidney microsomes were 20 mU and 25 U/rag protein, respectively. Thiobarbiturie acid-reactive material was assayed essentially as described (12) with a TBA-TCA-HC! reagent containing 3 mM BHA. A 500/zl sample of reaction mixture was mixed with 1.5 ml of the TBA-TCA-HCI reagent and was incubated at 85°C for 15 rain, followed by centri...

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Section: Vol 40 No 6 1996supporting

confidence: 84%

“…The significance of thiol-transition metal ligands in thiol-mediated LPO. Thiols should be considered as transition metal ligands in thiol-mediated LPO (19). Based on stop-flow kinetics and Mossbauer spectra, a complex of (Fe2+-GSH)202 has been suggested as the reactive species in the Fecatalyzed oxidation of GSH (20).…”

Section: Vol 40 No 6 1996mentioning

confidence: 99%

The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

1996

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“…It has been proposed that Fe-NTA can be easily activated by reducing agents including cysteine and y-glutamylcysteine. These reducing agents are amply supplied by the decomposition of glutathione within the lumen by the action of y-glutamyltranspeptidase and dipeptidase situated at the proximal tubular brush border membrane, thereby effectively promoted the membrane lipid peroxidation [12,21,22]. To determine the effect of Fe-NTA on the proteolytic and endocytotic functions of the kidney monitoring with k-FABP and ~2v-globulin as markers, rabbit polyclonal IgG against CX2u-globulin was raised and used for the immunochemical analysis of these proteins.…”

Section: Resultsmentioning

confidence: 99%

Acute nephrotoxicity of a carcinogenic iron chelate Selective inhibition of a proteolytic conversion of α_2U‐globulin to the kidney fatty acid‐binding protein

et al. 1995

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The mechanism of acute nephrotoxicity of an iron chelate in vivo has been investigated. Administration of a renal carcinogen ferric nitrilotriacetate (Fe-NTA) (15 mg Fe/kg body weight, intraperitoneally) led to selective loss of a renal protein with an apparent molecular mass of 17 kDa. Analysis of the 17 kDa protein by NH2-terminal sequence demonstrated its identity over 16 NH2-terminal residues as a kidney fatty acid-binding protein (k-FABP) that is a proteolytically modified form of a2u-globulin, a major urinary protein of adult male rats. An immunochemical study using anti-a2u-globulin polyclonal antibodies confirmed that a single injection of Fe-NTA led to a decrease in k-FABP levels. However, a 19-kDa protein identical to the C~zu-globulin progressively appeared in the kidney, suggesting that the proteolytic processing of azu-globnlin in the renal proximal tubules was suppressed by the treatment with Fe-NTA. By monitoring k-FABP and its precursor Ot2u-globulin , it was determined that repeated exposure to Fe-NTA caused suppression of both proteolytic and endocytotic activity of the kidney. The implications of these data in relation to the nephrotoxicity of Fe-NTA are discussed.renal carcinogenesis mediated by Fe-NTA treatment, the role of iron or Fe-NTA has not been fully established, except for the induction of lipid peroxidation. Okada and his co-workers have shown that membrane lipid peroxidation, as seen biochemically by 2-thiobarbituric acid-reactive substances (TBARS) and histochemically by cold Schiff's method (detection of aldehydes), is one of the basic mechanisms of Fe-NTAinduced renal injury and is closely associated with renal carcinogenesis [10][11][12][13][14]. It can therefore be assumed that these renal oxidative injuries are associated with the alteration of the fundamental functions of the kidney, including reabsorption of filtered proteins from glomerular ultrafiltrate and their proteolysis.In the present paper, based on the identification of a major kidney-specific protein, we demonstrate the alteration of proteolytic and endocytotic functions of the renal brush border membrane caused by Fe-NTA treatment. Materials and methods

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Li + d nuclear reaction

Saxena

1970

Proc. Indian Acad. Sci.

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Excited States of 8Be From the 7Li(d,n)8Be Reaction

Cited by 10 publications

References 3 publications

The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

Acute nephrotoxicity of a carcinogenic iron chelate Selective inhibition of a proteolytic conversion of α_2U‐globulin to the kidney fatty acid‐binding protein

Li + d nuclear reaction

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Excited States of 8Be From the 7Li(d,n)8Be Reaction

Cited by 10 publications

References 3 publications

The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

The role of chelators in the catalysis of glutathione‐γ‐glutamyl transpeptidase‐dependent lipid peroxidation by transition metals

Acute nephrotoxicity of a carcinogenic iron chelate Selective inhibition of a proteolytic conversion of α2U‐globulin to the kidney fatty acid‐binding protein

Li + d nuclear reaction

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Acute nephrotoxicity of a carcinogenic iron chelate Selective inhibition of a proteolytic conversion of α_2U‐globulin to the kidney fatty acid‐binding protein