The PI3K/Akt pathway is not a main driver in HDL-mediated cell protection

• Published in: Cellular signalling 2019-10, Vol.62, p.109347-109347, Article 109347
• Main Authors: Zheng, Adi, Dubuis, Gilles, Ferreira, Carla Susana Mendes, Pétremand, Jannick, Vanli, Güliz, Widmann, Christian
• Format: Article
• Language: English
• Subjects: Akt; Cell death; DLD-1; ER stress; HDLs; HUVEC; Min6; PI3K; Starvation
• ISSN: 0898-6568; 1873-3913
• DOI: 10.1016/j.cellsig.2019.109347

High-density lipoproteins (HDLs) can protect cells against a variety of death-inducing stresses. This is often accompanied by activation of the anti-apoptotic Akt kinase but whether this activation mediates the protective functions of HDLs is still unclear. In this study, we evaluated the roles of PI3K/Akt signaling in endoplasmic reticulum (ER) stress- and starvation-induced cell death using pharmacological and genetic approaches to gain a better understanding of the relationship between Akt- and HDL-mediated protection. Three cell models were used for this purpose, a primary endothelial cell line, an insulinoma cell line and a colon adenocarcinoma cell line. Our results show that HDLs indeed elicited mild Akt activation in all the tested cellular models. PI3K is one of the main upstream proteins involved in Akt stimulation. In the three cellular models, LY294002, a PI3K inhibitor, only slightly blunted HDLs protection, indicating that HDLs induce PI3K-independent cell protection. Furthermore, genetic ablation or silencing of Akt did not abolish the protective effects of HDLs. This study demonstrates that the PI3K-Akt signaling pathway is not the main mediator of the cell protective functions of HDLs. Further investigation is therefore needed to identify the intrinsic mechanism of HDL-mediated cell protection. •High-density lipoproteins (HDLs) protect Min6, DLD1, and HUVEC cells against ER stressors and against starvation.•HDLs stimulate Akt phosphorylation in these cells, but to low levels.•Pharmacological inhibition of PI3K, preventing HDL-mediated Akt activation, does not alter the protection conferred by HDLs.•Genetic down-regulation or inactivation of Akt1 and Akt2 in DLD1 or Min6 cells does not affect HDL-mediated protection.