Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.
Biochimie. 2018 Jun 05;:
Authors: Banerjee D, Sinha A, Saikia S, Gogoi B, Rathore AK, Das AS, Pal D, Buragohain AK, Dasgupta S
Abstract
The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger...

Source: Biochimie - June 5, 2018 Category: Biochemistry Authors: Banerjee D, Sinha A, Saikia S, Gogoi B, Rathore AK, Das AS, Pal D, Buragohain AK, Dasgupta S Tags: Biochimie Source Type: research