Flupirtine protects both neuronal cells and lymphocytes against induced apoptosis in vitro: Implications for treatment of AIDS patients

Müller, Wernér E.G.; Dobmeyer, Jürgen; Dobmeyer, Thomas S.; Pergande, G.; Perovic, Sanja; Leuck, Jürgen; Rossol, Rita

doi:10.1038/sj.cdd.4400206

Cited by 15 publications

(2 citation statements)

References 28 publications

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“…In this regard, it has been demonstrated that morphine can activate the TNFα and IL-6 promoters through NF-κB (Roy et al 1998). Most often, opioids by themselves are not intrinsically toxic but significantly contribute in neuronal toxicity leading to neuronal injury (Muller et al 1997). Morphine and other opioids have been shown to induce oxidative stress (OS) in the immune system as well as in the central nervous systems, which leads to the induction of TNFα (Bhat et al 2004).…”

Section: Introductionmentioning

confidence: 99%

TNF Alpha Production in Morphine-Treated Human Neural Cells Is NF-κB-Dependent

Sawaya

Deshmane

Mukerjee

et al. 2008

J Neuroimmune Pharmacol

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The cytokine tumor necrosis factor alpha (TNFalpha) is a key factor in several inflammatory diseases and its levels increase in response to a variety of internal or external stimuli. The regulation of the TNFalpha promoter is mediated by several transcription factors including the nuclear factor kappa B protein (NF-kappaB). This study examines the role of NF-kappaB in the regulation of TNFalpha production by morphine in microglia. Using reverse transcriptase polymerase chain reaction, we demonstrated the presence of morphine receptors in these cells. We next demonstrated the ability of morphine to promote TNFalpha production and secretion by these cells using a cytokine array assay. Transient transfection experiments led to the identification of the region located between nucleotides -751 and -615 within the TNFalpha promoter as being responsive to morphine treatment. The DNA sequence of this region contains a motif indicative of a potential NF-kappaB binding site. The use of a small interfering RNA directed against p65, a subunit of NF-kappaB, demonstrated that TNFalpha induction by morphine is NF-kappaB-dependent. All of the effects of morphine were reversed by the morphine inhibitor, naloxone. These data provide important insights into the effects of morphine on microglia.

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Section: Introductionmentioning

confidence: 99%

TNF Alpha Production in Morphine-Treated Human Neural Cells Is NF-κB-Dependent

Sawaya

Deshmane

Mukerjee

et al. 2008

J Neuroimmune Pharmacol

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“…Cells (0.5ϫ10 6 ) were cultured in 500 µl medium composed of MEM supplemented with 10 mM HEPES buffer, 2.6 % sodium bicarbonate, 0.1 U/ml penicillin, 0.1 U/ml streptomycin, 10 % FCS and 1 mM glutamine for 24 hours under 5 % CO 2 and 37°C [22].…”

Section: Patients and Methods S Blood Samplesmentioning

confidence: 99%

Unaltered apoptotic behaviour of mononuclear cells from patients with sporadic Creutzfeldt-Jakob disease

Ratzka¹,

Schröter²,

Cepek³

et al. 2001

J Neurol

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Creutzfeldt-Jakob disease (CJD) belongs to the group of transmissible spongiform encephalopathies. It is suspected that a pathologically altered form of the prion protein (PrPSc) is the decisive trigger of the disease. Data from animal experiments suggest an involvement of the lymphatic system in the intracorporal transport of PrPSc. However, it has not so far been possible to detect PrPSc on mononuclear cells (MNCs) either in the sporadic form of CJD or in the new variant of CJD (vCJD). In order to determine a possible alteration of MNCs in CJD, we investigated the natural and induced apoptotic behaviour of these cells. MNCs from 19 patients with sporadic CJD and from 20 patients with other neurological disorders were used. The cells were analysed by fluorescence cytometry with and without apoptosis induction by xanthine oxidase and hypoxanthine. The apoptosis rate was quantified using the stain 7-amino-actinomycin D (7-AAD). In the morphological investigation of the cells before apoptosis induction, there were no significant differences between the groups with regard to cell size and granularity of the MNCs. After apoptosis induction, the typical significant decrease in cell size and increase in granularity of the cells occurred in both groups. Significant differences between the patient populations were not found. For the first time, our investigation has demonstrated that a functional impairment of MNCs with regard to their apoptotic behaviour does not occur in sporadic CJD. It remains open to question whether this mechanism plays an important role in forms of transmissible encephalopathy other than sporadic CJD, especially after oral transmission.

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