Healthy Cell Traffic: Red Light, Red light, Turn to Green
Healthy cell traffic and communication matters. As many of us commute to and from throughout the day using various vehicles for transportation we often don’t think about our bodies own traffic system. We drive our cars from here to there and encounter traffic along the way never really pondering what is occurring on the inside with our very own traffic control system.
Did you know that our bodies, much like the roads we travel, have their own red light and green light systems designed to keep internal accidents or damage to a minimum?
This red light/green light system functions to stop and start incoming and outgoing signals, or messages.
Not unlike the number of commuters driving into a city during the morning rush hour, the volume of traffic moving into a cell is some 10 times higher than that of vesicles moving out.[1]
Epigenetics tells us that our DNA is not static and that our genes may be altered from external forces, or signals.
It has been said that…
“If you want to find the secrets of the universe, think in terms of energy, frequency and vibration.” – Nikola Tesla
Simply put, all signals are a form of frequency, or electromagnetic currency, constantly fluctuating depending on the environment one is exposed to.
If this is true, then the signal becomes paramount in relation to our Epigenetic expression of DNA, and the start/stop system imbedded within us becomes our very own traffic control system designed to maintain a safe internal environment for the highways and byways on the super pathways of our protein expression.
What can disrupt the signal?
Epigenetic Factors that Harm Healthy Cells
Some things we simply cannot avoid while occupying this vessel. Some things are just out of our control. For example, you cannot choose the air that you breathe.
I’ve written extensively on this subject in the past as it relates to Epigenetic factors impacting our cellular health.
Things like Electromagnetic Frequency Waves, Tracers (Clouds and Trails), and Heavy Metals are things that we cannot get away in this day and age. But, there are things we can do within our capacity to mitigate the damage.
Other things such as the food we choose to consume are absolutely within our control.
Environmental influences, such as a person’s diet and exposure to pollutants, can impact the epigenome.
The epigenome is a multitude of chemical compounds that can tell the genome what to do. An epigenome consists of a record of the chemical changes to the DNA and histone proteins of an organism; these changes can be passed down to an organism’s offspring via transgenerational epigenetic inheritance.
Exposure to environmental toxins can literally alter our DNA and those changes can be passed down to our children with some studies reporting up to fourteen generations. Genetic mutations disrupt the function of a gene, whereas epigenetic defects typically misregulate gene expression through altering the DNA, RNA, and Proteins.
Some Epigenetic Factors may include, but are not limited to:
- Electromagnetic Frequency Waves (EMF)
- Tracers – Clouds and Trails
- Heavy Metals
- Pesticides & Herbicides
- Dioxins
- Processed Foods
- Personal Care & Cleaning Products
- Viral & Bacterial Infections
- Contaminated Water
Other factors listed may be avoided and attenuated for through constant and diligent practice of paying close attention to the products you choose to purchase and the habits you choose to incorporate on a daily basis.
There are certain things that are in your immediate control. However, some factors simply cannot be avoided due to the world we now live in.
Healthy Cell Signaling
If our cells do not communicate properly, much like a marriage, they get divorced, and are no longer healthy cells.
Cell signaling is part of any communication process that governs the basic activities of healthy cells and coordinates all healthy cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis.
Errors in signaling interactions and cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes.
By understanding unhealthy and healthy cell signaling, diseases may be treated more effectively.[2]
Knowing when to “inhibit” a signal can be extremely beneficial. On the flip side, knowing when to “upregulate” a signal also has its advantages. Equally as important, oftentimes we don’t want to do either rather we want to “modulate” the signal. Why?
Life is about balance. The ebb and flow. When we speak of modulating a signal, or a gene, we are seeking only to regulate its function in terms of balancing it. You’ve probably heard that sometimes too much of a good thing is bad. This speaks to moderation, or in this regard to cellular function, modulation.
So what is our cellular trafficking system, or what I like to call the stop/start system?
Red Light, Red Light Turn to Green
Phosphatases and kinases are our body’s red light/green light system in relation to cellular trafficking. There is also vesicle-mediated trafficking but that is another topic for another time.
Phosphatase enzymes are essential to many biological functions because phosphorylation (e.g. by protein kinases) and dephosphorylation (by phosphatases) serve diverse roles in cellular regulation and signaling.
Whereas phosphatases remove phosphate groups from molecules, kinases catalyze the transfer of phosphate groups to molecules from ATP. Together, kinases and phosphatases direct a form of post-translational modification that is essential to the healthy cell’s regulatory network.[3]
In contrast to kinases, phosphatase enzymes recognize and catalyze a wider array of substrates and reactions. For example, in humans, Serine/Threonine kinases outnumber Ser/Thr phosphatases by a factor of ten.[4]
Phosphatases remove the phosphate group, which is essential if the system of intracellular signaling is to be able to reset for future use.
The tandem work of kinases and phosphatases constitute a significant element of the healthy cell’s regulatory network.[5]
While there are thousands of protein kinases and phosphatases we could touch on, some take higher precedence over others as it relates to the impact their malfunction has to our health.
In this respect, in order not to completely confuse the reader, we shall only talk about one….for now.
PP2A is involved in multiple regulatory processes, such as DNA replication, metabolism, transcription, and development.
Protein Phosphatase 2A (PP2A)
In a 2018 study titled “The serine/threonine protein phosphatase 2A controls autoimmunity[6]” they describe the function of PP2A in relation to autoimmune disease and that “targeting PP2A in T cell subsets may be therapeutic for SLE and other autoimmune diseases.”
This is an indication that when this signal does not get turned off it can create an unchecked “overreaction” that may lead to various autoimmune diseases.
This is like you running a red light with oncoming traffic at an intersection.
In yet another study we find that “mounting evidence suggests that inhibition of protein phosphatase-2A (PP2A), a serine/threonine phosphatase, could enhance anticancer immunity.”[7]
The fact is that if our signals are not maintained in a healthy ebb and flow state of the currency, then we manifest an extremely large subset of dis-eased states.
Again here we see that…
“There are a large number of signaling pathways responsible for transmitting information within the healthy cell. Although cellular signaling is thought to be majorly governed by protein kinases ‘cascade effects’; their antagonists’ protein phosphatases also play a crucial dual role in signal transduction. By dephosphorylating the proteins involved in signaling pathways, phosphatases may lead to their activation and sometimes they may terminate a signal generated by kinases activity. Due to counterbalancing the function of phosphorylation, the protein phosphatases are very important to signal transduction processes and thus the control of phosphatase activity is as significant as kinases, in the regulation of a plethora of cellular processes.”[8]
The de-regulation of PP2A is not only implicated in autoimmune settings, but in some specific pathologies such as Cancer, Heart diseases, Neurodegenerative disorders, Diabetes, and Chronic Obstructive Pulmonary Disease to say the least.
To further add to the importance of the red light/green light system in relation to PP2A according to one paper “All roads lead to PP2A”.[9]
Master Regulator & Gatekeeper
Keeping PP2A in check is paramount in any dis-ease setting.
According to a study titled “PP2A as a master regulator of the healthy cell cycle[10]” we see that PP2A is involved in regulating almost all major pathways and healthy cell cycle checkpoints.
Furthermore, in the same study, we see that “PP2A is a gatekeeper from mitotic entry to mitotic exit.”
Mitosis a type of cell division, or splitting of cells to generate a copy, or new cell from the blueprint of the latter. Essentially, it is how we regenerate on a cellular basis.
This makes PP2A acting as the “gatekeeper” kind of a big deal!
The Broken Off Switch
Signal transduction is a dynamic process involving both “On” and “Off” switches.
For example, a 2016 study titled “The broken “Off” switch in cancer signaling: PP2A as a regulator of tumorigenesis, drug resistance, and immune surveillance[11]” they mention that:
“Activating mutations of RAS or PI3K can be viewed as the switch being stuck in the “On” position resulting in continued signaling by survival and/or proliferation pathway. On the other hand, inactivation of protein phosphatases such as the PP2A family can be seen as the defective “Off” switch that similarly can activate these pathways.”
So, in other words, a broken off switch can have the same impact as a broken on switch and can activate pathways that lead to disease if left unchecked.
Think of it in terms of a car battery. If the car hasn’t been started in a long time it will drain the battery and the car won’t start. On the flip side, if you had an electrical surge, like an electromagnetic pulse (EMP) it would fry it.
Protein phosphatases serve as the “brakes” for most if not all cellular signaling cascades.
In this regard making sure the brake pads are at optimal functioning capacity so you don’t end up in a cellular car accident is vital.
PP2A Modulators in a Healthy Cell
Aside from pharmaceutical use in relation to PP2A modulators, I believe natural compounds should be the first line of defense.
Since time immemorial, natural products have been the backbone of the traditional system of healing throughout the globe, and have also been an integral part of history and culture.
Up to 50% the approved drugs during the last 30 years are from either directly or indirectly from natural products and in the area of cancer, over the time frame from around the 1940s to date, of the 175 small molecules 85 actually being either natural products or directly derived therefrom.
The use of plants as medicines has a long history in the treatment of various diseases. The plant-derived compounds have a long history of clinical use, better patient tolerance, and acceptance. To date, 35,000-70,000 plant species have been screened for their medicinal use.[12]
Natural Extracts Affect on PP2A Methylation
A small library of approximately 30 natural extracts was created using isopropanol based extraction methods at 65°C. These extracts were assayed for their ability to preserve the methylation status of PP2A AC dimer in the presence of protein phosphatase methylesterase-1, or PME-1, using a radioactive filter binding assay. Data were collected in triplicate and the IC50 value was determined via the four parameter logistic curve fit using SigmaPlot graphical software. Results indicate a distinction between extract categories where the seed and root, bark and leaf categories consistently prevented PP2A demethylation with an IC50 better than 5 µg/mL.
https://cdn2.hubspot.net/hubfs/4515283/Blog/Imported_Blog_Media/Articles20140930160157_PhosphataseConference_2014-1.pdf
Other Natural PP2A Modulators for a Healthy Cell:
- Honokiol/Magnolol [R]
- Forskolin [R]
- α-Tocopheryl succinate [R]
- EHT™ [R]
- Propolis [R]
- Blue/Green algae [R]
In summary, communication of the cell with its environment is crucial for all tissue and organ function. Kinase and phosphatase activities have been shown to control both general and cargo-specific trafficking.
PP2A is involved in metabolism, mitochondria function, molecular trafficking, cell division, cytoskeleton, DNA replication, DNA repair, components of actin, microtubule, Golgi and nucleopore, regulators of cellular signaling, metabolism, and mitochondria function.
The vast majority of protein phosphorylation occurs on specific serine and threonine residues that are oppositely regulated by protein kinases and phosphatases.
Kinases and phosphatases control much of our cellular trafficking systems in order to maintain a healthy balance of ebb and flow.
Knowing where the rubber meets the road to regulate our cellular trafficking system is paramount on your journey from better to best!
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Sources:
[1] https://www.nature.com/articles/nature12408?draft=journal&proof=trueIn
[2] https://en.wikipedia.org/wiki/Cell_signaling
[3] https://en.wikipedia.org/wiki/Phosphatase
[4] https://stke.sciencemag.org/content/6/275/rs10
[5] https://www.worldcat.org/title/fundamentals-of-biochemistry-life-at-the-molecular-level/oclc/892195795
[6] https://www.ncbi.nlm.nih.gov/pubmed/28736280
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5974350/
[8] https://www.ncbi.nlm.nih.gov/pubmed/30170071
[9] https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13573
[10] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4905575/
[11] https://www.sciencedirect.com/science/article/pii/S2214647416300320
[12] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3560124/
