What is ER stress in cells?

Endoplasmic reticulum stress (ER stress) occurs when proteins are not properly folded or conformed (misfolded protein). ER stress interferes with normal physiological functions of the cell and the response of cells to ER stress is called unfolded protein response (UPR).

How do cells recover from ER stress?

The ESR acts to restore normal ER homeostasis and is therefore cytoprotective. However, when a stress is so strong or persistent that ER dysfunction cannot be corrected, metazoan cells can initiate apoptosis, allowing the regulated destruction of cells that are irreparably damaged or a risk to the organism as a whole.

What diseases are caused by ER stress?

There is accumulating evidence implicating prolonged ER stress in the development and progression of many diseases, including neurodegeneration, atherosclerosis, type 2 diabetes, liver disease, and cancer.

Does oxidative stress cause ER stress?

As the protein folding process is dependent on redox homeostasis, the oxidative stress can disrupt the protein folding mechanism and enhance the production of misfolded proteins, causing further ER stress.

How does ER stress affect other organelles?

Toxic accumulation of ROS within ER and mitochondria disturbs fundamental organelle functions. Sustained ER stress is known to potentially elicit inflammatory responses via UPR pathways. Additionally, ROS generated through inflammation or mitochondrial dysfunction could accelerate ER malfunction.

How can we prevent ER stress?

Weight loss has beneficial effects. It reduces ER stress in man, together with a decrease of triglycerides in adipose tissue and liver, and blood glucose and insulin concentrations (64). The activation of nuclear receptors could also modify the effect of the diet on lipids and glucose.

How do you detect ER stress?

ER stress can be measured indirectly by monitoring the activation/upregulation of various components of the endogenous UPR. Typically this involves using qRT-PCR or immunoblotting techniques to detect changes in UPR mRNA and protein levels, respectively [6].

How endoplasmic stress and cell death could cause type 2 diabetes?

ER stress may also link obesity and insulin resistance in type 2 diabetes. High fat feeding and obesity induce ER stress in liver, which suppresses insulin signaling via c-Jun N-terminal kinase activation. In vitro data suggest that ER stress may also contribute to cytokine-induced beta-cell death.

What is a stress inhibitor?

ER stress inhibitors such as tauroursodeoxychloic acid (TUDCA; Xie et al., 2002; Ozcan et al., 2006) and salubrinal (Boyce et al., 2005) are generally used to suppress ER stress. TUDCA is a known ER stress inhibitor as a chemical chaperone that stabilizes the structure of proteins (Xie et al., 2002).

What does tunicamycin do to cells?

Tunicamycin (Tun), a naturally occurring antibiotic, induces ER stress in cells by inhibiting the first step in the biosynthesis of N-linked glycans in the proteins resulting many misfolded proteins [16].