The Opposite Effects of ROCK and Src Kinase Inhibitors on Susceptibility of Eukaryotic Cells to Invasion by Bacteria Serratia grimesii

AbstractBacterial internalization into eukaryotic cells is ensured by a sophisticated interplay of bacterial and host cell factors. Being a part of cell environment, opportunistic intracellular bacteria have developed various mechanisms providing their interaction with cell surface receptors (E-cadherin, integrins, epidermal growth factor receptor), activation of components of eukaryotic signaling pathways, and facilitation of bacterial uptake, survival, and intracellular replication. Our previous studies on the mechanisms underlying penetration of the opportunistic bacteriaSerratia grimesii into cultured eukaryotic cells have shown that pretreatment of the cells with N-acetylcysteine (NAC) promotesS. grimesii invasion, and this effect correlates with the upregulation of E-cadherin expression. Since NAC has been shown to regulate expression of both Src kinase and ROCK, the aim of this work was to reveal the role of these kinases inS. grimesii invasion. We demonstrated that Y-27632, a specific inhibitor of ROCK, significantly promoted invasion of cultured eukaryotic cells byS. grimesii. On the other hand, invasion of the same cells byS. grimesii was inhibited with the Src kinase inhibitor Src-I1 and siRNA directed against RhoA. The effects of the inhibitors correlated with the corresponding changes in the E-cadherin gene expression, upregulation by the ROCK inhibition and downregulation by the Src kinase inhibition. These results prove the participation of ROCK and Src protein...
Source: Biochemistry (Moscow) - Category: Biochemistry Source Type: research