Statins induce microautophagy in RAW 264.7 cell line. (APP3P.107)

Abstract

Abstract Autophagy is process by which cells recycle cellular components to overcome starvation. This process is constitutive in antigen presenting cells such as dendritic cells and macrophages. Among the various autophagy pathways, microautophagy (Mi) has a unique significance as it is implicated in the biogenesis of exosomes which are relevant to the design of therapeutics. Statins have been shown to up regulate macroautophagy and alleviate the effect of LPS apart from inhibiting cholesterol synthesis. However their role in microautophagy has not been reported. In the present study we investigated the effect of statins on microautophagy using the RAW264.7 cell line as a model system. Treatment with statins resulted in an up regulation of the genes for MA as well as Mi as determined by qPCR. Further studies showed that the levels of proteins TSG101 and VPS4 were increased during statin treatment. Pretreatment with statins led to a lowering of LAMP2A levels and decreased LAMP2A on the late endosomes, mimicking a LAMP2A knock down. Pretreatment with statins not only lowered the transcription of iNOS and TNF-alpha genes but also prevented the effect of LPS by decreasing initial levels of LAMP2A and increasing levels of TSG101. We propose that Mi can be a surrogate for Chaperone mediated autophagy (CMA) under conditions where the components of CMA are rendered non-functional due to disruption in normal cellular metabolism.