BCL2

The BCL2 gene encodes a protein called apoptosis regulator Bcl-2 [R].

This protein helps determine when it’s time for cells to die through a process called apoptosis. Cells undergo apoptosis when they have reached the end of their natural life cycle, when they become damaged, or if they mutate [R].

The Bcl-2 protein triggers cell death by disrupting the mitochondrial membrane [R].

Mutations in the BCL2 gene have been associated with:

• High blood sugar [R]
• High blood pressure [R]
• Grey matter volume (brain size) [R]
• Male-pattern baldness [R]
• Autoimmune disease [R]
• Cancer [R]

Bcl-2 is closely linked to cancer because of its effect on cell death. Tumors grow if cells do not undergo apoptosis when they should. If some cells start to grow and divide unaffected by Bcl-2 mediated apoptosis signals, those cells can form potentially cancerous tumors [R, R].

Suppresses apoptosis in a variety of cell systems including factor-dependent lymphohematopoietic and neural cells. Regulates cell death by controlling the mitochondrial membrane permeability. Appears to function in a feedback loop system with caspases. Inhibits caspase activity either by preventing the release of cytochrome c from the mitochondria and/or by binding to the apoptosis-activating factor (APAF-1). May attenuate inflammation by impairing NLRP1-inflammasome activation, hence CASP1 activation and IL1B release (PubMed:17418785).

What Does The BCL2 Gene Do?

The BCL2 gene is activated whenever cells experience stress or damage. When activated, this gene basically acts as a signal that tells the damaged cell not to self-destruct, so that it keeps itself alive while it waits to get repaired by other mechanisms [R].

In other words, this gene protects cells from dying off too quickly due to oxidative stress, inflammation, or even strokes and other serious physical injuries to the brain [R, R].

BCL2 and Blood Pressure

The BCL2 gene codes for B cell lymphoma 2 (bcl-2), a protein that promotes the survival and division of cells by suppressing programmed cell death (apoptosis) [R]. 

Cell proliferation and programmed cell death are two opposing processes that play major roles in the structural changes of tissues. Studies have shown that an imbalance in these processes within heart muscle cells and blood vessel muscle cells may contribute to decreased tissue density [R, R, R].

Specifically, elevated programmed cell death may drastically lower the number of small blood vessels (arterioles and capillaries). This can increase the resistance of larger blood vessels (arteries) to blood flow, raising blood pressure and leading to secondary conditions such as heart failure [R, R].

Variants of BCL2 have been associated with high blood pressure (hypertension). These variants may lower the production of bcl-2, resulting in excessive cell death and blood flow resistance [R, R].

BCL2 and Male-Pattern Baldness

Bcl-2 may be essential for regulating the hair growth cycle, in which hair grows within a follicle, detaches from the follicle, and falls out. Cell growth and expansion (proliferation) and cell death must remain balanced in order for this cycle to be maintained [R]. 

In line with this, bcl-2 production has been reported to be increased during hair growth and decreased during hair detachment [R]. 

Interestingly, mice that lack bcl-2 experience slower rates of hair growth, while mice that produce excess bcl-2 experience accelerated hair loss — suggesting that bcl-2 must remain balanced for normal hair cycling [R].

Variants of BCL2 have been associated with male-pattern baldness. These variants may dysregulate the production of bcl-2, resulting in hair cycle perturbation [R, R, R, R].

BCL2 and Blood Sugar

Bcl-2 is a protein well-known to regulate cell death by tightening the barrier of a part of the cell called the mitochondria. In this manner, bcl-2 can prevent the mitochondria from releasing proteins that can stimulate cell death [R].

The mitochondria also plays vital roles in generating the energy-carrying compound ATP. In cells of the pancreas, ATP is essential for the release of insulin, a hormone that regulates blood sugar levels [R]. 

When insulin needs to be released in large amounts (for example, after eating a large meal), the demand for pancreatic cells to generate ATP may be increased to such an extent that these cells may begin to release toxic proteins from their mitochondria. This may eventually lead to the death of pancreatic cells [R]. 

Pancreatic cell death has been linked to elevated blood sugar levels and type 1 diabetes. Similarly, excess insulin release has been linked to elevated blood sugar and type 2 diabetes, as high insulin levels experienced over a prolonged period of time can result in decreased insulin receptor sensitivity [R].

Recent studies have provided evidence that bcl-2 may be able to act on the mitochondria to suppress the excess release of insulin and prevent the death of pancreatic cells [R].  

Indeed, a variant of BCL2 has been associated with elevated blood sugar. This variant may decrease the production or activity of bcl-2 in the pancreas, which may result in excess insulin release and pancreatic cell death [R].

For example, in patients who suffered from brain damage, higher levels of BCL2 activity were associated with better chances of survival and better overall cognitive function after recovery: most likely because their brain was able to keep more of its neurons alive so that they could be repaired [R].

In general, you might think that higher levels of BCL2 would be better, since this helps keep cells alive. However, recall that part of the reason our cells come with pre-programmed “death switches” is to ensure that damaged or mutated cells can be disposed of safely without turning cancerous [R]. Therefore, because BCL2 suppresses cell death, elevated levels of BCL2 could also potentially increase long-term risk of tumor formation (tumorigenesis) [R, R, R].

For example, one study observed higher levels of BCL2 in healthy breast tissue from women who had previously survived a diagnosis of breast cancer compared to women who never had cancer [R]. Although it’s still not known to what degree BCL2 levels might be directly involved in cancer development, this early finding provides suggestive evidence for a link that will have to be followed up by future studies [R, R, R].

Because of its dual role, at the end of the day what you really want is to have this gene in balance! Having too little of it could make your brain more vulnerable to oxidative stress and other sources of cell damage; but too much of it could make you more susceptible to cancer in the long run.

The Cognitive Effects Of BCL2

Just like any other cell in your body, your brain’s neurons are also vulnerable to stress, and have to be either repaired or disposed of when they’re damaged. Because BCL2 plays a key role in the repair processes that keep your neurons healthy, variants that affect how this gene works may influence how well your brain is able to carry out complex cognitive processes.

For example, SNPs in BCL2 have been associated with overall cognitive function, fluid intelligence, learning and memory, processing speed, and cognitive flexibility [R, R, R].

This gene has also been associated with increased brain size (grey matter volume) in several key brain areas involved in higher cognitive processes, such as the striatum and the hippocampus. This increase in brain size probably reflects the role of BCL2 in keeping neurons alive when they are damaged, which over time would result in having more neurons overall (and therefore a relatively larger brain). This association between BCL2 and brain size probably explains some of the relationships between this gene and various different aspects of cognition [R, R, R].