Crocin protects human embryonic kidney cells (HEK293) from α- and β-Zearalenol-induced ER stress and apoptosis.
α-zearalenol (α-ZOL) and β-zearalenol (β-ZOL) are the major metabolites of Zearalenone (ZEN) and are known to induce many toxic effects. In the present study, we investigated the involvement of endoplasmic reticulum (ER) stress in α- and β-ZOL-mediated toxicity in human kidney cells (HEK293) and evaluated the effect of a common dietary compound Crocin (CRO), from saffron. We show that α- and β-ZOL treatment induces ER stress as evidenced by the upregulation of the 78 kDa glucose-regulated protein (GRP78) and the Growth arrest and DNA damage-inducible protein (GADD34). Activation of the ER stress response is associated with activation of the mitochondrial pathway of apoptosis. This apoptotic process is characterized by an increase in ROS generation and lipid peroxidation, a loss of mitochondrial transmembrane potential (ΔΨm) and activation of caspases. We also demonstrate that the antioxidant properties of CRO help to prevent ER stress and reduce α- and β-ZOL-induced apoptosis in HEK293 cells. Our results suggest that saffron consumption might be helpful to prevent α- and β-ZOL-induced ER stress and toxicity.
Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia.|Faculty of Sciences of Bizerte, Carthage University, Tunis, Tunisia.
Intidhar
I
Ben Salem
Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia.|Faculty of Sciences of Bizerte, Carthage University, Tunis, Tunisia.
Manel
M
Boussabbeh
INSERM UMR-S 769, LabEx LERMIT, Châtenay-Malabry, France.
Alexandre
A
Prola
INSERM UMR-S 769, LabEx LERMIT, Châtenay-Malabry, France.
Arnaud
A
Guilbert
Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia.
Hassen
H
Bacha
INSERM UMR-S 769, LabEx LERMIT, Châtenay-Malabry, France.|Université Paris-Sud, Faculté de Pharmacie, Châtenay-Malabry, France.|Université de Versailles Saint Quentin en Yvelines, Versailles, France.
Christophe
C
Lemaire
Laboratory for Research on Biologically Compatible Compounds (LRSBC), Faculty of Dental Medicine, Rue Avicenne, 5019, Monastir, Tunisia. salwaabid@yahoo.fr.
Salwa
S
Abid-Essefi
D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D057809:HEK293 Cells; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D015029:Zeranol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity
D000975:Antioxidants; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D006360:Heat-Shock Proteins; D008565:Membrane Proteins; D020011:Protective Agents; C018551:glucose-regulated proteins; C029659:zearalenol; D002338:Carotenoids; D015029:Zeranol; C029036:crocin; D020169:Caspases
Apoptosis; Crocin; Endoplasmic reticulum stress; Oxidative stress; α-Zearalenol; β-Zearalenol