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

Jinyong Huang,Tianming Teng,Qing Yang,Longfei Huang,Zhelong Xu,Yuchen Xue,Yuemin Sun,Bo Bian

doi:10.32604/biocell.2021.015917

Abstract

Zinc is a trace element involved in maintaining cellular structure and function. Although zinc is associated with left ventricular hypertrophy (LVH), there have been few reports on this association. This study aimed to evaluate the correlation between Zip14 and expression of endoplasmic reticulum stress (ERS) associated molecules in hypertrophied 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-binding protein 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 by Inductively Coupled Plasma Optical Emission Spectroscopy. The results indicated that compared with the Control group, Zip14 mRNA and protein expression in LVH rat hearts were markedly increased (P < 0.01). Zinc content in rat 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 LVH rat hearts (P < 0.05, P < 0.01). Linear regression models showed that Zip14 mRNA expressions were positively correlated 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.

Highlights

Zinc is a trace element involved in maintaining cellular structure and function (Ryul et al, 2015)
The mean systolic blood pressure (SBP) and mean diastolic blood pressure (DBP) were significantly increased in the left ventricular hypertrophy (LVH) group compared with the Control group at week 18
Body weight (BW) was lower in the LVH group compared with the Control group (P < 0.05) at week 18

Summary

Introduction

Zinc is a trace element involved in maintaining cellular structure and function (Ryul et al, 2015). High zinc levels have irreversible effects on proteins and lead to the dysfunction of many proteins. Low levels of zinc are detrimental to cells because it is a cofactor for more than 300 enzymes and 2000 transcription factors, as well as mediating cell signaling (Roshanravan et al, 2015; Huang et al, 2017). The balance of intracellular zinc concentration, termed zinc homeostasis, is critical. When intracellular zinc is deficient, ER stress (ERS) occurs, causing dysfunction of the ER. Zinc is necessary to maintain normal ER function. ERS and cell dysfunction can be induced by oxidative stress and acute ischemia-reperfusion (IR) injury (Zhang, 2010; Zhang et al, 2014a; Zhang et al, 2014b)

Objectives

Methods

Results

Conclusion