N-acetylcysteine attenuates TNF-alpha induced changes in secretion of interleukin-6, plasminogen activator inhibitor-1 and adiponectin from 3T3-L1 adipocytes.
TNF-alpha is a key molecule in obesity-related metabolic disturbances. This study was designed to determine whether N-acetylcysteine (NAC), an antioxidant, prevents the activation of nuclear factor-kappaB (NF-kappaB) by exogenously administered TNF-alpha in adipocytes, and whether such change affects the production of adipocytokines. The treatment of well-differentiated 3T3-L1 cells with 20 mM of NAC significantly increased the reduced glutathione concentration up to 150% of control. The treatment with 10 ng/ml of TNF-alpha decreased antioxidant enzyme levels such as CuZn-superoxide dismutase (SOD), MnSOD and catalase, and activated NF-kappaB in 3T3-L1 adipocytes. The activation of NF-kappaB was significantly prevented by the pretreatment with 20 mM of NAC. TNF-alpha (1-10 ng/ml) dose-dependently increased interleukin (IL)-6 and plasminogen activator inhibitor-1 (PAI-1) secretion from 3T3-L1 adipocytes, while decreased adiponectin secretion. NAC (5-20 mM) attenuated the TNF-alpha-induced changes in these adipocytokine secretions in a dose-dependent manner. The effect of TNF-alpha and NAC on the adipocytokine productions was exerted at the m-RNA level, judging from results of the real time RT-PCR analysis. The present study revealed that NAC inhibited the TNF-alpha-mediated activation of NF-kappaB and improved the adverse changes in the levels of IL-6, PAI-1 and adiponectin in 3T3-L1 adipocytes. NAC may have the potential to improve the obesity-related abnormal adipocytokine metabolism by attenuating the TNF-alpha-induced oxidant-antioxidant imbalance in adipocytes.
Araki
Shunsuke
S
Department of Pediatrics, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, 807-8555, Japan.
Dobashi
Kazushige
K
Kubo
Kazuyasu
K
Yamamoto
Yukiyo
Y
Asayama
Kohtaro
K
Shirahata
Akira
A
D041721:3T3-L1 Cells / Q000187:drug effects; D000111:Acetylcysteine / Q000494:pharmacology*; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000378:metabolism; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D052242:Adiponectin; D000975:Antioxidants; D015850:Interleukin-6; D016328:NF-kappa B; D017395:Plasminogen Activator Inhibitor 1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D002374:Catalase; D013482:Superoxide Dismutase; D005978:Glutathione; D000111:Acetylcysteine