ROS signaling and ER stress in cardiovascular disease

Abstract

The endoplasmic reticulum (ER) produces the vast majority of all proteins secreted into the extracellular space, including hormones and cytokines, as well as cell surface receptors and other proteins which interact with the environment. Accordingly, this organelle controls essentially all vital links to a cell's external milieu, responding to systemic metabolic, inflammatory, endocrine, and mechanical stimuli. The central role the ER plays in meeting protein synthetic and quality control requirements in the face of such demands is matched by an extensive and versatile ER stress response signaling network. ROS mediate several critical aspects of this response. Nox4, an ER resident capable of producing ROS, acts as a proximal signaling intermediate to transduce ER stress-related conditions to the unfolded protein response, a homeostatic corrective mechanism. However, chronic ER stress caused by unrelenting internal or external demands produces a secondary rise in ROS, generally resulting in cell death. Sorting out the involvement of ROS at different levels of the ER stress response in specific cell types is key to understanding the molecular basis for chronic diseases such as atherosclerosis, hypertension, and diabetes. Here, we provide an overview of ER stress signaling with an emphasis on the role of ROS.

Fuziline alleviates isoproterenol‐induced myocardial injury by inhibiting ROS‐triggered endoplasmic reticulum stress via PERK/eIF2α/ATF4/Chop pathway

“…B, Quantitative analysis of mean DCFH-DA fluorescence intensity in different groups using bar graphs. 11,14 It has been reported that ISO causes myocardial injury possibly by damaging mitochondrial function via altering mitochondrial membrane permeability and increasing production of ROS. D, Quantitative analysis of apoptotic cells in different groups using bar graphs.…”

“…9,10 Among these, excessive accumulation of ROS could cause severe oxidative stress injury directly leading to cell death. 13,14 Hence, inhibiting ER stress-induced apoptosis maybe an effective way to alleviate myocardial injury. 11 A series of studies have shown that apoptosis in myocardial injury is also associated with endoplasmic reticulum (ER) stress injury.…”

Long non‐coding RNA MEG3 knockdown attenuates endoplasmic reticulum stress‐mediated apoptosis by targeting p53 following myocardial infarction

“…Previous studies have indicated that reactive oxygen species (ROS) are produced as a downstream event of ERS that can lead to cell death . We detected the ROS levels in hypoxic NMVMs by the dihydroethidium (DHE) assay.…”

“…Previous studies have indicated that reactive oxygen species (ROS) are produced as a downstream event of ERS that can lead to cell death. 26 We detected the ROS levels in hypoxic NMVMs by the dihydroethidium (DHE) assay. Pretreatment with lenti-si lncRNA MEG3 reduced the increased number of DHE-positive NMVMs that were induced by hypoxia, indicating lower ROS levels (Figure 4E,F).…”

Icariside II prevents hypertensive heart disease by alleviating endoplasmic reticulum stress via the PERK/ATF-4/CHOP signalling pathway in spontaneously hypertensive rats

“…The main purpose of the UPR is to restore endoplasmic reticulum function and promote cell survival; however, continuous or severe ERS activates apoptotic signalling, leading to apoptosis . Protein kinase R‐like endoplasmic reticulum kinase (PERK) is a transmembrane signal transducer of the endoplasmic reticulum and most closely related to oxidative stress . PERK promotes the over‐expression of CCAAT/enhancer binding protein homologous protein (CHOP) through activating transcription factor‐4 (ATF‐4), leading to apoptosis.…”