Nifedipine protects against overproduction of superoxide anion by monocytes from patients with systemic sclerosis

Autor: Allanore , Yannick, Borderie , Didier, Périanin , Axel, Lemaréchal , Hervé, Ekindjian , Ohvanesse Garabed, Kahan , André
Přispěvatelé: Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de biochimie et de génétique moléculaire [CHU Cochin], Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by a grant from the Association des Sclérodermiques de France., Maylin, Françoise, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )
Jazyk: angličtina
Rok vydání: 2005
Předmět:
MESH : Oxidative Stress
Male
systemic sclerosis
MESH : Aged
MESH: Calcium Channel Blockers
MESH: Monocytes
MESH : Calcium Channel Blockers
Antioxidants
Monocytes
MESH : Phosphorylation
Superoxides
MESH : Female
Phosphorylation
Cells
Cultured
Protein Kinase C
MESH: Aged
[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
MESH : Recombinant Fusion Prote
MESH: Oxidative Stress
MESH: Middle Aged
Middle Aged
Calcium Channel Blockers
MESH : Nifedipine
[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
monocyte
MESH : Antioxidants
Tetradecanoylphorbol Acetate
Female
MESH: Nifedipine
Research Article
MESH: Cells
Cultured
Nifedipine
MESH : Male
Recombinant Fusion Proteins
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
[ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system
MESH: Recombinant Fusion Prote
MESH : Cells
Cultured
Humans
MESH : Middle Aged
MESH : Protein Kinase C
[SDV.BC] Life Sciences [q-bio]/Cellular Biology
MESH : Protein Processing
Post-Translational
Aged
MESH: Drug Evaluation
Scleroderma
Systemic
MESH: Humans
MESH: Phosphorylation
[ SDV.BC ] Life Sciences [q-bio]/Cellular Biology
MESH : Humans
MESH: Antioxidants
MESH: Protein Kinase C
MESH: Male
MESH : Drug Evaluation
Oxidative Stress
MESH : Monocytes
MESH: Protein Processing
Post-Translational
Drug Evaluation
superoxide anion
Protein Processing
Post-Translational
MESH: Female
Zdroj: Arthritis Research and Therapy
Arthritis Research and Therapy, BioMed Central, 2005, 7, pp.R93-100. ⟨10.1186/ar1457⟩
Arthritis Research and Therapy, 2005, 7, pp.R93-100. ⟨10.1186/ar1457⟩
Arthritis Research & Therapy
Arthritis Research and Therapy, BioMed Central, 2005, 7, pp.R93-100. 〈10.1186/ar1457〉
ISSN: 1478-6354
DOI: 10.1186/ar1457⟩
Popis: We have reported previously that dihydropyridine-type calcium-channel antagonists (DTCCA) such as nifedipine decrease plasma markers of oxidative stress damage in systemic sclerosis (SSc). To clarify the cellular basis of these beneficial effects, we investigated the effects in vivo and in vitro of nifedipine on superoxide anion (O2*-) production by peripheral blood monocytes. We compared 10 healthy controls with 12 patients with SSc, first after interruption of treatment with DTCCA and second after 2 weeks of treatment with nifedipine (60 mg/day). O2*- production by monocytes stimulated with phorbol myristate acetate (PMA) was quantified by the cytochrome c reduction method. We also investigated the effects in vitro of DTCCA on O2*- production and protein phosphorylation in healthy monocytes and on protein kinase C (PKC) activity using recombinant PKC. After DTCCA had been washed out, monocytes from patients with SSc produced more O2*- than those from controls. Nifedipine treatment considerably decreased O2*- production by PMA-stimulated monocytes. Treatment of healthy monocytes with nifedipine in vitro inhibited PMA-induced O2*- production and protein phosphorylation in a dose-dependent manner. Finally, nifedipine strongly inhibited the activity of recombinant PKC in vitro. Thus, the oxidative stress damage observed in SSc is consistent with O2*- overproduction by primed monocytes. This was decreased by nifedipine treatment both in vivo and in vitro. This beneficial property of nifedipine seems to be mediated by its cellular action and by the inhibition of PKC activity. This supports the hypothesis that this drug could be useful for the treatment of diseases associated with oxidative stress.
Databáze: OpenAIRE
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