Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

Mitochondrial ROS govern the LPS-induced pro-inflammatory response in microglia cells by regulating MAPK and NF-κB pathways

“…We next examined whether LPS-induced mitochondrial ROS are involved in the activation of NF-B, an important component of the pro-inflammatory response, in activated microglia [7,9]. Our results demonstrate that Mito-TEMPO treatment leads to a decrease in the levels of LPS-induced phosphorylation of IB, an inhibitor of NF-B activation (Fig.…”

“…Other reports suggest that regulation of LPS-induced mitochondrial ROS is involved in the pro-inflammatory response of BV-2 microglia cells via NF-B activation [7,22]. We, therefore, examined whether mitochondrial ROS affect the LPS-induced MAPK and NF-B signal pathways by using Mito-TEMPO.…”

“…Apart from serving as an antimicrobial defense in microglia cells, ROS are key factors in immune cell signaling [15]. Mitochondrial ROS are implicated in the pro-inflammatory responses of microglia cells [7,22]. In addition, various treatments that induce mitochondrial ROS result in enhanced activation of inflammation transcription factors [6,8].…”

Dual Role of Superoxide Dismutase 2 Induced in Activated Microglia

“…Therefore, the overall levels of ROS can be effectively reduced by eliminating superoxide. Activated microglia produce superoxide predominantly from NADPH oxidase, although ROS generation from mitochondria has also been reported (10,11). Of note, once ROS are generated anywhere within cells, further ROS generation is induced via uncoupling of the mitochondrial respiratory chain, known as ROS-induced ROS release (46).…”

“…Mitochondria are another source of ROS inside activated microglia. Copper chloride has been shown to stimulate mitochondrial superoxide production in murine BV-2 microglial cells (10). Lipopolysaccharide (LPS), an endotoxin found in the outer membrane of Gram-negative bacteria, also elicits mitochondrial superoxide production, which is regulated by the mitochondrial chaperone glucose-regulated protein 75 (Grp75/mortalin) (11).…”