Endoplasmic reticulum stress associated apoptosis as a novel mechanism in indoxyl sulfate‑induced cardiomyocyte toxicity.

Abstract:

:Indoxyl sulfate (IS), a typical uremic toxin, is of great importance in the development of chronic kidney disease. In addition to its nephrotoxicity, previous studies have provided increasing evidence for its cardiovascular toxicity. The mechanism underlying IS‑induced cardiovascular toxicity has been elusive to date. The present study aimed to evaluate whether IS treatment could induce apoptosis of H9C2 cells, and used the endoplasmic reticulum (ER) stress‑modulator 4‑phenylbutyric acid (4‑PBA) to evaluate whether IS‑induced apoptosis is indeed associated with ERS. To evaluate whether IS induces apoptosis in H9C2 cardiomyocytes, cells were exposed to increasing concentrations of IS (500, 1,000, and 2,000 µM) for 24 h, and apoptosis was detected by flow cytometry. To determine whether IS‑induced apoptosis is associated with ERS, cells were divided into 4 groups: control group, PBA group, IS group and PBA+IS group. IS dose‑dependently induced apoptosis, and increased the expression of ER chaperones in H9C2 cells. Additionally, 4‑PBA treatment decreased IS‑induced apoptosis, and reduced ERS‑associated protein expression induced by IS. Therefore, the mechanism may be associated with the CCAAT‑enhancer‑binding protein homologous protein and c‑Jun N‑terminal kinase signaling pathways.

journal_name

Mol Med Rep

authors

Tan X,Cao XS,Zhang P,Xiang FF,Teng J,Zou JZ,Ding XQ

doi

10.3892/mmr.2018.9496

subject

Has Abstract

pub_date

2018-12-01 00:00:00

pages

5117-5122

issue

6

eissn

1791-2997

issn

1791-3004

journal_volume

18

pub_type

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