ApoA-I natural variant G26R triggers a pro-inflammatory response in murine macrophages.

RAMELLA, N.; ROSU, S. A.; SCHINELLA, G; RIOS, J. L.; ANDUJAR, I.; RIMOLDI. O. J.; TRICERRI, M. A.

Congreso; XII Panamerican Association of Biochemistry and Molecular Biology; 2013

Panamerican Association of Biochemistry and Molecular Biology

Human apolipoprotein A-I (apoA-I) is the major protein in High Density Lipoprotein particles (HDL) and plays a principal role in the Reverse Cholesterol Transport and endothelial function. Some apoA-I natural variants, like G26R, are involved in systemic amyloidosis, affecting different organs and with variable severity. We previously reported that apoA-I G26R is less stable than the Wild Type protein (Wt) under physiological conditions, and that the inflammatory scenery can induce pro-amiloidogenic processing in both Wt and G26R. Here we set out to answer whether this variant can trigger an inflammatory response as part of the pathogenic pathways. We show that apoA-I G26R induces the release of Reactive Oxigen Species (ROS) and the pro-inflammatory cytokines TNF-alpha and IL-1B from murine macrophages in vitro. Moreover, we obtain similar results in the Nitric oxide production, cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS). Interestingly, macrophage activation was not evident under the same experiment conditions when incubated with other apoA-I amiloidogenic variant (Lys 107-0). Altogether these results show that several mechanisms, involving protein stability and cellular activation are involved with different depth in apoA-I induced amyloidosis.