Upregulation of Zip14 correlates with induction of endoplasmic reticulum stress (ERS) in hypertrophied hearts of Dahl salt-sensitive rats

[摘要] Zinc is a trace element involved in maintaining cellular structure and function. Although zinc is associated withleft ventricular hypertrophy (LVH), there have been few reports on this association. This study aimed to evaluate thecorrelation between Zip14 and expression of endoplasmic reticulum stress (ERS) associated molecules inhypertrophied hearts of rats. Dahl salt-sensitive rats were fed a high salt diet to establish a left ventricular hypertrophy(LVH) rat model. RT-PCR was used to determine Zip14, activating transcription factor (ATF4), ATF6, x-box-bindingprotein 1 (xBP1), C/EBP homologous protein (CHOP), immunoglobulin-binding protein (BiP) mRNA expression.Western blotting was used to evaluate Zip14, BiP, CHOP, GAPDH expression. Zinc levels were measured byInductively Coupled Plasma Optical Emission Spectroscopy. The results indicated that compared with the Controlgroup, Zip14 mRNA and protein expression in LVH rat hearts were markedly increased (P < 0.01). Zinc content inrat heart tissue was significantly increased in the LVH group compared with the Control group (P < 0.05). ATF4,ATF6, xBP1 mRNA expressions were increased in LVH rat hearts compared with Control hearts (P < 0.001).Compared with the Control group, CHOP and BiP mRNA and protein expression were markedly increased in LVHrat hearts (P < 0.05, P < 0.01). Linear regression models showed that Zip14 mRNA expressions were positivelycorrelated with zinc concentration, ATF4 and ATF6 mRNA expressions in Control hearts (P = 0.0005, P = 0.0052,P = 0.0026, respectively) and LVH rat hearts (P < 0.0001, P = 0.0119, P = 0.0033, respectively). In conclusion,upregulation of Zip14 in LVH rat hearts correlated with zinc accumulation and induction of ERS.

[学科分类] 仪器

[关键词] Zinc;Zip14;Endoplasmic reticulum stress (ERS);Left ventricular hypertrophy (LVH);Rat hearts