A kinase anchor protein 1 in rheumatoid arthritis status of promoter methylation and mitochondrial dysfunction

Abstract

Rheumatoid Arthritis (RA), a chronic, inflammatory, autoimmune disorder with multiple articular and extra-articular manifestations deeply effectuates social and economic well being of those affected. Mitochondrial activity is important for survival and activation of different cells including those contributing to pathogenesis of RA by metabolic actions and signalling pathways. The present study highlighted the relationship between oxidative stress, mitochondrial function and inflammation, and their interplay with A Kinase Anchor Protein 1 (AKAP1), Nuclear factor erythroid 2 related factor 2 Kelch like ECH associated protein 1 (Nrf2 Keap1) signaling, Glutathione peroxidase 3 (GPx3) as well as relevance of these relationships to disease severity, in light of different cells. Mitochondrial dysfunction is dependent upon regulatory mechanisms in cells depending on stress/physiological conditions. Reduced cell-specific activities of respiratory chain specific activities of respiratory chain enzymes correlated significantly to disease activity and enzymes correlated significantly to disease activity and cytosolic/mitochondrial ROS levels. No significant differences cytosolic/mitochondrial ROS levels. No significant differences were observed in methylation of promoter region of AKAP1, NRF2, KEAP1and GPx3. Analysis of mononuclear cells from peripheral blood unraveled the expression of AKAP1, Nrf2 and peripheral blood unraveled the expression of AKAP1, Nrf2 and Steroidogenic acute regulatory (StAR) proteins indicating their importance as they had positive correlation with disease activity, inflammatory and hormonal mark disease activity, inflammatory and hormonal markers. Altered CD8+ and Regulatory T cells presented negative correlation to disease activity in patients. This study gives pointers in disease activity in patients. This study gives pointers in direction of new targets with opportunities for therapy or direction of new targets with opportunities for therapy or biomarkers related to clinical indications.