Cellular stress and disease

The critical role of psychological and physical stress in disease manifestation is becoming more clear. Both clinical and molecular data demonstrating that increased stress is associated with (but not limited to) the following:

– Short term memory loss
– Depression
– Suppressed immune system
– Obesity
– Heart disease

While one should practice proper stress management, our bodies feel stress in a way many of us cannon conceive — at the cellular level. Increasing number of publications in peer-reviewed journals are making the connection between a specific type of cellular stress–endoplasmic reticulum stress–and a long list of diseases:

ER stress-related diseases

ER stress-related diseases

– Stroke
– Heart disease
– Type 1 diabetes
– Type 2 diabetes
– Cancer
– Autoimmune disease
– Alzheimer’s disease
– Parkinson’s disease
– Prion disease (cause of mad cow disease)
– Bipolar disease
–  Atherosclerosis
– Amyotrophic lateral sclerosis
– Polyglutamine disease

The Cell

The Cell


What is the endoplasmic reticulum?
Our cells are compartmentalized  with designated functions involving the maintenance and replication of the cell. A vital compartment (organelle) positioned adjacent to the nucleus is the endoplasmic reticulum responsible for protein synthesis, protein folding, and protein transport (preparing the molecular machines within your cells). It is also responsible for the production and storage of steroids, glycogen, and other molecules.

What happens when the endoplasmic retuculum gets stressed? When stressed, this cellular compartment no longer functions as intended, causing a buildup of unfolded proteins. Because proteins are the workhorses of your cells, the cell halts new proteins synthesis and responds to alleviate this problem with a series of powerful signals (unfolded protein response). This process reprograms the cell through altered gene expression and cellular signaling, which can lead to disease.

How is cellular stress associated with disease? While some of these cellular stress–disease links are simply correlations, researchers have identified specific mechanisms for others, such as:

– Heart disease: increased cellular stress leads to degeneration of cardiac muscle cells.
– Type 1 diabetes: Wolcott-Rallison syndrome
– Type 2 diabetes: increased cellular stress leads to insulin resistance

Factors that increase cellular stress:
– Hypoxia (reduced blood flow to tissues)
– Build up of oxidants
– Glucose deprivation (ketogenic diet, aka Atkins diet)
– High-fat diets
– Viral infections

While we cannot control all cellular processes, there are some lifestyle considerations. 1) Get plenty of exercise to aid blood flow and oxygen delivery. Exercise will in turn cause a significant increase in free radicals (increased oxygen consumption) so, 2) consume a balanced diet (forget the low-carb routine) that is rich in antioxidants. 3) Stay away from fatty foods.

This research also provides us with hope for novel therapeutics as the mechanisms of cellular stress-based disease manifestation is better understood.

Reference:
Inki Kim, Wenjie Xu & John C. Reed
Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities.
Nature Reviews Drug Discovery
7, 1013-1030 (December 2008)

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