Saura-Esteller 2021 Int J Mol Sci
|Saura-Esteller J, Sánchez-Vera I, Núñez-Vázquez S, Cosialls AM, Gama-Pérez P, Bhosale G, Mendive-Tapia L, Lavilla R, Pons G, Garcia-Roves PM, Duchen MR, Iglesias-Serret D, Gil J (2021) Activation of the integrated stress response and ER stress protect from fluorizoline-induced apoptosis in HEK293T and U2OS cell lines. Int J Mol Sci 22:6117.|
Saura-Esteller Jose, Sanchez-Vera Ismael, Nunez-Vazquez Sonia, Cosialls Ana M, Gama-Perez Pau, Bhosale Gauri, Mendive-Tapia Lorena, Lavilla Rodolfo, Pons Gabriel, Garcia-Roves Pablo M, Duchen Michael R, Iglesias-Serret Daniel, Gil Joan (2021) Int J Mol Sci
Abstract: The prohibitin (PHB)-binding compound fluorizoline as well as PHB-downregulation activate the integrated stress response (ISR) in HEK293T and U2OS human cell lines. This activation is denoted by phosphorylation of eIF2α and increases in ATF4, ATF3, and CHOP protein levels. The blockage of the activation of the ISR by overexpression of GRP78, as well as an increase in IRE1 activity, indicate the presence of ER stress after fluorizoline treatment. The inhibition of the ER stress response in HEK293T and U2OS led to increased sensitivity to fluorizoline-induced apoptosis, indicating a pro-survival role of this pathway after fluorizoline treatment in these cell lines. Fluorizoline induced an increase in calcium concentration in the cytosol and the mitochondria. Finally, two different calcium chelators reduced fluorizoline-induced apoptosis in U2OS cells. Thus, we have found that fluorizoline causes increased ER stress and activation of the integrated stress response, which in HEK293T and U2OS cells are protective against fluorizoline-induced apoptosis.
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Cell death, Oxidative stress;RONS Organism: Human Tissue;cell: Lymphocyte Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET Pathway: ROX HRR: Oxygraph-2k