Biofactors - Volume 10, issue 2-3

Authors: Goossens, Vera | De Vos, Kurt | Vercammen, Dominique | Steemans, Margino | Vancompernolle, Katia | Fiers, Walter | Vandenabeele, Peter | Grooten, Johan

Article Type: Research Article

Abstract: TNF is produced during inflammation and induces, among other activities, cell death in sensitive tumour cells. We previously reported an increased generation of ROS in TNF‐treated L929 fibrosarcoma cells prior to cell death. These ROS are of mitochondrial origin and participate in the cell death process. Presently, we focus on the identification of parameters that control ROS production and subsequent cytotoxicity. From the cytotoxic properties and susceptibility to scavenging of TNF‐induced ROS as compared to pro‐oxidant‐induced ROS we conclude that TNF‐mediated ROS generation and their lethal action are confined to the inner mitochondrial membrane. Oxidative substrates, electron‐transport inhibitors, glutathione and …thiol‐reactive agents but also caspase inhibitors modulate TNF‐induced ROS production and imply the existence of a negative regulator of ROS production. Inactivation of this regulator by a TNF‐induced reduction of NAD(P)H levels and/or formation of intraprotein disulfides would be responsible for ROS generation. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 145-156, 1999

Authors: Mohamed, Abdel Khalek | Bierhaus, Angelika | Schiekofer, Stephan | Tritschler, Hans | Ziegler, Reinhard | Nawroth, Peter P.

Article Type: Research Article

Abstract: A common endpoint of hyperglycemia dependent cellular changes is the generation of reactive oxygen intermediates (ROIs) and the presence of elevated oxidative stress. Therefore, oxidative stress is supposed to play an important role in the development of late diabetic complications. Formation of advanced glycation end products (AGE’s) due to elevated nonenzymatic glycation of proteins, lipids and nucleic acids is accompanied by oxidative, radical‐generating reactions and thus represents a major source for oxygen free radicals under hyperglycemic conditions. Once formed, AGE’s can influence cellular function by binding to several binding sites including the receptor for AGE’s, RAGE. Binding of AGE’s (and …other ligands) to RAGE results in generation of intracellular oxidative stress and subsequent activation of the redox‐sensitive transcription factor NF‐\kappa B in vitro and in vivo. Consistently, activation of NF‐\kappa B in diabetic patients correlates with the quality of glycemic control and can be reduced by treatment with the antioxidant \alpha ‐lipoic acid. The development of techiques allowing for a tissue culture independent measurement of NF‐\kappa B activation in patients with diabetes mellitus gives insights into the molecular mechanisms linking diabetes mellitus and hyperglycemia with formation of advanced glycated endproducts and generation of oxidative stress finally resulting in oxidative stress mediated cellular activation. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 157-167, 1999

Authors: Jacob, S. | Rett, K. | Henriksen, E.J. | Häring, H.‐U.

Article Type: Research Article

Citation: Biofactors, vol. 10, no. 2-3, pp. 169-174, 1999

Authors: Böl, Gaby‐Fleur | Tewes, Frank | Brigelius‐Flohé, Regina

Article Type: Research Article

Abstract: Stimulation of the Interleukin‐1 receptor type I (IL‐1‐RI) with IL‐1 activates an associated serine/threonine kinase, IRAK, which phosphorylates downstream targets, resulting in NF\kappa B activation. The signaling cascade is accompanied by oxidative processes and contains putative targets for redox regulation. Preincubation of the murine T cell line EL‐4 and the human umbilical cord vein endothelial cell line ECV 304 with thiol modifying compounds like diamide, menadione or phenylarsine oxide inhibited the IL‐1‐induced phosphorylation of an endogenous substrate with a molecular mass of 60 kD. In the endothelial cell line, a second target of about 85 kD was phosphorylated after …IL‐1 stimulation, which was also inhibited by thiol modification. These data suggest that IL‐1 signal transduction depends on free thiols which might be targets for redox regulation not only in lymphocytes, but also in endothelial cells. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 175-178, 1999

Authors: Blanco, B. | Ferrández, M.D. | Correa, R. | Del Rio, M. | Guaza, C. | Hernanz, A. | De la Fuente, M.

Article Type: Research Article

Abstract: The administration of the thiol compounds, N‐acetylcysteine (NAC) and in particular thioproline (thiazolidine‐4‐carboxylic acid) at 0.1% w/w concentration in the diet, improves lymphocyte functions in old female Swiss mice, as has been shown in our previous studies. In the present work, adult mice from two different strains, namely BALB/c (an inbred strain) and OF1‐Swiss (noninbred strain), were fed a diet supplemented with the above dose of each thiol compound jointly for five weeks. At 28 weeks of age, peritoneal cell suspensions were obtained and different steps of the phagocytic process, the most representative activity of macrophages, as well as interleukin‐1\beta …(IL‐1\beta ) production, were studied. Thus, adherence to substrate, mobility directed to a chemoattractant gradient (chemotaxis), ingestion of inert particles and superoxide anion production were analysed. The results show that diet supplementation with NAC plus thioproline increased all macrophage functions studied with the exception of superoxide anion production, which was decreased. These effects were more evident in macrophages from Swiss mice, whereas in BALB/c mice the stimulation of phagocytosis and IL‐1\beta production was lower and no differences were seen after treatment in adherence and superoxide anion production. These data suggest that immune function can be improved in adult mice by administration of the above thiol compounds, especially in the noninbred strain of OF1‐Swiss mice. Show more

Keywords: Thioproline, N‐acetylcysteine, macrophages, phagocytic function, interleukin‐1\beta

Citation: Biofactors, vol. 10, no. 2-3, pp. 179-185, 1999

Authors: Molina‐Holgado, F. | Hernanz, A. | de la Fuente, M. | Guaza, C.

Article Type: Research Article

Abstract: The pathological mechanisms that cause central nervous system (CNS) dysfunction in most neurological diseases are not well established. Theiler’s murine encephalomyelitis virus (TMEV) is known to interact with cells of the CNS and its intracerebral inoculation to susceptible mice strains causes neurological disorders resembling multiple sclerosis (MS). In this study, we reported that primary astrocyte cultures from SJL/J susceptible mice when infected with TMEV released important amounts of nitrites (NO_{2}^{-} ) to the culture medium, as measured in the supernatants 24 hours after infection. In addition, we observed an increment in the production of tumour necrosis factor alpha (TNF‐\alpha …) by susceptible SJL/J strain derived astrocytes infected with TMEV. The treatment with the thiolic antioxidant N‐acetyl‐cysteine partially suppressed the virus‐stimulated production of nitric oxide and TNF‐\alpha, in a dose response fashion. These results indicate that during viral infection astrocytes are an important cellular source of nitric oxide and TNF‐\alpha , substances which play important roles during CNS inflammatory events. The effects of the antioxidant N‐acetyl‐cysteine, modulating the production of the above compounds by TMEV‐infected astrocytes may be a significant factor in preventing CNS demyelination. Show more

Keywords: N‐acetyl‐cysteine, nitric oxide, tumour necrosis factor‐\alpha, Theiler’s virus, astrocyte cultures

Citation: Biofactors, vol. 10, no. 2-3, pp. 187-193, 1999

Authors: Correa, R. | Blanco, B. | Del Río, M. | Víctor, V. | Guayerbas, N. | Medina, S. | De la Fuente, M.

Article Type: Research Article

Abstract: A previous study has shown that diet supplementation with thioproline (thiazolidine‐4‐carboxylic acid, TCA), an intracellular sulfhydril antioxidant and free radical scavenger, stimulates lymphocyte functions in old mice. In the present work, the effect of thioproline ingestion on the phagocytic functions of peritoneal macrophages, namely adherence, chemotaxis, phagocytosis and superoxide anion production was studied in adult female OF1‐Swiss mice, that were fed thioproline (0.1% w/w) for five weeks, starting this ingestion at the age of 22 \pm 2 weeks. Mice were divided into a fast and a slow group based on their exploratory activity, which was assessed by their …performance in a T‐shaped maze. Slow mice showed a worse phagocytic activity with respect to fast animals. After thioproline treatment, a stimulation of all the functions studied as well as a neutralization of the superoxide radical were observed. The effect of this antioxidant was stronger in the slow than in the fast group. Thus, a diet supplemented with thioproline may enhance the immune functions, especially when they are depressed. Show more

Keywords: Thioproline, macrophages, phagocytic function, ageing

Citation: Biofactors, vol. 10, no. 2-3, pp. 195-200, 1999

Authors: Duine, Johannis A.

Article Type: Research Article

Abstract: Glutathione is not a universal coenzyme for formaldehyde oxidation. MySH (mycothiol, 1‐O‐(2' ‐[N‐acetyl‐L‐cysteinyl]amido‐2' ‐deoxy‐\propto ‐D‐glucopyranosyl)‐D‐myo‐inositol) is GSH’s counterpart as coenzyme in formaldehyde dehydrogenase from certain Gram‐positive bacteria. However, formaldehyde dissimilation and detoxification not only proceed via thiol‐dependent but also via thiol‐independent dehydrogenases. The distinct structures and enzymatic properties of MySH‐dependent and GSH‐dependent formaldehyde dehydrogenases could provide clues for development of selective drugs against pathogenic Mycobacteria. It is to be expected that other new types of thiol‐dependent formaldehyde dehydrogenases will be discovered in the future. Indications exist that the product of thiol‐dependent formaldehyde oxidation, the thiol formate ester, …is not only hydrolytically converted into thiol and formate but can also be oxidatively converted in some cases by a molybdoprotein aldehyde dehydrogenase into the corresponding carbonate ester, decomposing spontaneously into CO_{2} and the thiol. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 201-206, 1999

Authors: Rhee, Sue Goo | Kang, Sang Won | Netto, Luis E. | Seo, Min Seok | Stadtman, Earl R.

Article Type: Research Article

Citation: Biofactors, vol. 10, no. 2-3, pp. 207-209, 1999

Authors: Sherman, David R. | Mdluli, Khisimuzi | Hickey, Mark J. | Barry, III, Clifton E. | Stover, C. Kendall

Article Type: Research Article

Abstract: The Mycobacterium tuberculosis AhpC is similar to a family of bacterial and eukaryotic antioxidant proteins with alkylhydroperoxidase (Ahp) and thioredoxin‐dependent peroxidase (TPx) activities. AhpC expression is associated with resistance to the front‐line antitubercular drug isoniazid in the naturally resistant organisms E. coli and M. smegmatis. We identified several isoniazid‐resistant M. tuberculosis isolates with ahpC promoter mutations resulting in AhpC overexpression. These strains were more resistant to cumene hydroperoxide than were wild‐type strains. However, these strains were unchanged in their sensitivity to isoniazid, refuting a role for AhpC in detoxification of this drug. All the isoniazid‐resistant, AhpC‐overexpressing strains were also deficient …in activity of the mycobacterial catalase‐peroxidase KatG. KatG, the only known catalase in M. tuberculosis, is required for activation of isoniazid. We propose that compensatory ahpC promoter mutations are selected from KatG‐deficient, isoniazid‐resistant M. tuberculosis during infections, to mitigate the added burden imposed by organic peroxides on these strains. Show more

Citation: Biofactors, vol. 10, no. 2-3, pp. 211-217, 1999