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. 2013 Jul 19;15(3):131–137. doi: 10.1179/174329210X12650506623483

The effect of hypoxia mimetic cobalt chloride on the expression of EC-SOD in 3T3-L1 adipocytes

Tetsuro Kamiya 1, Hirokazu Hara 2, Naoki Inagaki 3, Tetsuo Adachi 2
PMCID: PMC7067344  PMID: 20594416

Abstract

It is well known that adipose tissue is not only a passive reservoir for energy storage but also produces and secretes a variety of bioactive molecules called adipocytokines, including adiponectin and tumor necrosis factor-α (TNF-α). Recently, it has been reported that adipose tissue can suffer a chronic hypoxic condition during hypertrophy of adipocytes, and this condition leads to the dysregulation of adipocytokines. Further, hypoxic adipocytes are in an increased oxidative stress. Extracellular-superoxide dismutase (EC-SOD) is an anti-inflammatory enzyme that protects cells from reactive oxygen species (ROS) by scavenging superoxide anion. Previous reports showed that plasma EC-SOD levels in type 2 diabetes patients were significantly and inversely related to the body mass index, homeostasis model assessment-insulin resistance index; however, the mechanisms of EC-SOD and adiponectin reductions during hypoxia remain poorly understood. Here, we demonstrate that cobalt chloride (CoCl2), a hypoxia mimetic, decreases EC-SOD and adiponectin in 3T3-L1 adipocytes by intracellular ROS-independent, but TNF-α and c-jun N-terminal kinase (JNK)-dependent mechanisms. From these results, it is possible that TNF-α is a key regulator of the reduction of EC-SOD and adiponectin in CoCl2-treated 3T3-L1 adipocytes, and we speculated that the reduction of EC-SOD and adiponectin would lead to and/or promote metabolic disorders.

Keywords: EXTRACELLULAR-SUPEROXIDE DISMUTASE, ADIPONECTIN, TUMOR NECROSIS FACTOR-ALPHA, C-JUN N-TERMINAL KINASE, COBALT CHLORIDE

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