Proinflammatory cytokines downregulate connexin 43-gap junctions via the ubiquitin-proteasome system in rat spinal astrocytes

摘要: Astrocytic gap junctions formed by connexin 43 (Cx43) are crucial for intercellular communication between spinal cord astrocytes. Various neurological disorders associated with dysfunctional Cx43-gap junctions. However, the mechanism modulating in astrocytes under pathological conditions is not entirely clear. A previous study showed that treatment of culture pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) decreased both Cx43 expression junction (GJIC) via a c-jun N-terminal kinase (JNK)-dependent pathway. The current further elaborates intracellular decreases an inflammatory condition. Cycloheximide chase analysis revealed TNF-α (10 ng/ml) alone or combination IFN-γ (5 ng/ml) accelerated degradation protein cultured reduction GJIC induced mixture were blocked pretreatment proteasome inhibitors MG132 (0.5 μM) epoxomicin (25 nM), significantly increased activity ubiquitination. In addition, IFN-γ-induced activation ubiquitin-proteasome systems was prevented SP600125, JNK inhibitor. Together, these results indicate JNK-dependent system condition disrupts astrocytic function, leading to dysfunction maintenance neuroinflammatory state.