Mitochondria get nasty when they get hurt

This is the full text of a very dense little article with a lot of gold embedded in it:

Mitochondrial reactive oxygen species drive proinflammatory cytokine production

Mitochondria are an appropriate fascination for any science writer who covers neurology, immunology, inflammation, or intracellular mechanisms — so here’s the BioWizardry primer on mitochondria.

Good primer from this article, in sci-speak:

“Mitochondria generate ATP through aerobic respiration, whereby glucose, pyruvate, and NADH are oxidized, thus generating ROS [Reactive Oxygen Species, or free radicals] as a byproduct. In normal circumstances, the deleterious effects caused by the highly reactive nature of ROS are balanced by the presence of antioxidants, including glutathione, carotenoids, and antioxidant enzymes such as catalase and glutathione peroxidase.”

Here’s a bit more insight into these fabulous little factories, gleaned from this article (which otherwise focuses on the mechanisms of a rare condition called TRAPS.)

The reason for the antioxidants we take so much of to support our overloaded nervous systems is, they act specifically against reactive oxygen species, ROS. ROS are chemically reactive molecules which contain oxygen, and use the oxygen to wreak a certain amount of biological havoc. As the BioWizardry mitochondria primer mentions, mitochondria are the biggest consumers and the biggest producers of antioxidants, and the nerve and muscle cells have the biggest population of mitochondria. Therefore, when your nervous system is under siege, as in chronic pain or anxiety or lupus or MCS or what-have-you, your body may need far more antioxidants than you can get in your food to support all those mitochondria, so they can keep making energy for your cells to use in their work.

“High levels of reactive oxygen species (ROS) are observed in chronic human diseases such as neurodegeneration, Crohn’s disease, and cancer. In addition to the presence of oxidative stress, these diseases are also characterized by deregulated inflammatory responses, including but not limited to proinflammatory cytokine production. New work exploring the mechanisms linking ROS and inflammation find that ROS derived from mitochondria act as signaltransducing molecules that provoke the up-regulation of inflammatory cytokine subsets via distinct molecular pathways.”

OK, so, the mitochondria (the biggest producers and the biggest users of antioxidants) generate a specific set of ROS which trigger inflammatory cytokines.

That means, pissed-off mitochondrial cells trigger pain.

Mitochondria get pissed off by being damaged and not being able to clean themselves up:

“Mitophagy is a specialized form of autophagy that refers to the specific catabolism of mitochondria. Pharmacological inhibition of autophagy by treatment of macrophages with 3-methyladenine resulted in the accumulation of damaged mitochondria and an increase in the net amount of mtROS…”

(Autophagy is the word for when the damaged/unhealthy cell consumes itself so the damage is cleaned up and their contents get recycled for healthy cells. Cells are all about the greater good. When they’re too damaged to do their jobs, they recycle themselves.)

AND this happens whether autophagy is prevented upstream or midstream:

“Thus, autophagy regulates baseline mtROS production from individual mitochondria by a yet to be identified mechanism.”

Mind you, only so many mitochondria can autophage at a time. When damage exceeds the cell’s ability to keep up with the housework, you have a lot of damaged mitochondria.
dyed  microscopic image of busted mitochondria showing the inner reticulated membrane
So, take care of those mitochondria.

More on antioxidants will be coming soon. Naturally, it’s not as simple as it looks.

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News flash: the gut and brain are connected!

The obvious scatological humor will be left alone. Guys, you know what I mean. (Girls who were outnumbered by your brothers, you too.)

I started to blog this article because the forehead-smacking tone of the revelation that the gut might relate to the brain was a bit too much for me. On closer examination, it looks like the misplaced drama is the writer’s, not the scientists’.

One of the places where serotonin is released is in the gut, where it helps digest proteins. That’s the most obvious “duh” moment here. Moreover, as those of us who remember our embryology know, the inter-relationships and constant correspondence between neurology and gut, gut and immunity, immunity and endocrine system, endocrine and neurological system are all too intense and interlocked for words.

Most studies make brutally clear that these so-called systems are medically treated as separate and distinct, but our bodies never got that memo. It’s all the same system, as far as the body is concerned.

Much of this researcher’s recent work focuses on neurology of the gut — enteric neurology. It’s a real thing now. His prior work focused on the biological environment in the gut, or the intestinal microbiota.

// START Word geek goes wild:
Sometimes, I just love medical terminology for the way it rolls, hops, and bounces off the tongue. Enteric neurology. Intestinal microbiota. Hypothalamic-pituitary-adrenal axis.

Maybe that last one doesn’t work so well.
// END Word geeking.

If you can stand the medical and chemical jargon, it’s worth looking into some of his work. It’s probably not a stretch to call it prescient, in that it is likely to lay the foundations for our emerging understanding of the gut as a more complex and self-managing, yet interlocked, set of systems than we’ve ever imagined before.

I can’t find the original science article, just this unsatisfactory and superficial overview. It says that intestinal microbiota affect the person’s mood and feelings, and that it’s possible to deliver specific probiotics (like yogurt species, naturally-fermented cole slaw, certain cheeses and the like) in order to have a specific benefit to the neurological system.

If you were an empiricist, like me, it would sound like “eating good, living food leads to better mental health,” which healers have been saying for millenia. But far be it from me to steal such well-researched thunder.

Link list:

Science Daily article:
A Gut-Full of Probiotics for Your Neurological Well-Being

Credentials of lead researcher, Prof. Lyte:
Mark Lyte, Ph.D., M.S., MT (ASCP)

Wikipedia’s digest (sic) of the enteric nervous system (this seems basically congruent with the uber-geeky medical studies I looked at on the subject, so I accept it as a decent primer):
Enteric Nervous System

Couldn’t find a good overview that didn’t involve more dead rodents than I could, er, stomach.

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Proportional monocytes and CRPS, translated

Today’s translation from medspeak to English: Inflammatory white blood cells and inflammatory nerve cells, in relation to CRPS.

Elevated blood levels of inflammatory monocytes (CD14+ CD16+ ) in patients with complex regional pain syndrome

Here’s what the jargon means.
// ed. note: my comments and clarifications are picked out by those two slashes and the contraction for “editorial notation.”

One important factor in CRPS is inflammation that starts in the nerves. Microglia and astrocytes, which are the inflammatory and immune cells of the nervous system, get active enough to cause worse pain by themselves.

That’s a sparking astrocyte. Pretty, eh?

// ed. note:  The inflammatory and immune responses are mixed blessings throughout the body.  An immune response is uncomfortable; think about the last time you had the flu — sucked, huh?  An inflammatory response can cause pain due solely to the inflammation, like with some kinds of arthritis.  So, for the microglia and astrocytes to make pain worse is not a surprise, since that’s what immune response and inflammation can do anywhere.

One type of immune cells normally floating in your blood, called monocytes, can get into the brain and spinal cord and turn themselves into the nervous system’s immune cells, microglia. The added level of inflammatory/immune response leads to more pain.

// ed. note: Again, not as strange as it sounds.  The body’s living cells all contain complete DNA, and they are designed to be both helpful and appropriate; heart cells transplanted into muscles become muscle cells, and muscle cells transplanted in the heart become very much like heart cells.  So, for this type of small white blood cells to turn into microglia is reasonable.

These are microglia in various active states.

// ed. note: The inflammatory response releases cytokines.  Cytokines are the chemical widgets, produced in inflammation, that serve as the chemical messengers running around the cells screaming that the sky is falling.  Some cytokines increase inflammatory pain, some cytokines reduce it.

This study looked for particular kinds of inflammatory monocytes in the blood, to test the assumption that higher levels of these particular types of monocytes (which can then turn into microglia, making the inflammation and pain worse, etc.) are related specifically to CRPS.

Now here’s the fun part.  The basic blood-borne indicators of inflammation and illness were no different in those with CRPS than in normal people. That’s why conventional lab results, like “complete” blood counts, come back normal for us.  However, the proportion of the particular types of monocytes associated with CRPS, were significantly higher in those with CRPS.  The type of cytokine that reduces inflammatory pain, was also significantly lower in people with CRPS.

That means the inflammatory process screws us coming and going, and screws specifically us, the people with CRPS, in ways that can be checked in a lab.

OK, GTK.

These are sensible scientists: they state that they don’t know if the monocyte proportions changed before or after the onset of CRPS, or both before and after.  If before, it might indicate a predisposition to CRPS, in which case surgeries and accidents have to be handled with specific care for antioxidant therapy and aggressive pain control. If after, it might be relevant in figuring out how things are going and if what the doc is doing works.

Also, some drug company could make a staggering fortune off of new meds that mess with this process. They actually mention that at the end of the article, which means someone has to fund their work.

// ed. note: Be fair. We have a profit-based health care system driven by enormous corporations that are traded on the stock exchange, and the Sarbanes-Oxley laws mean that their first obligation is to their shareholders. Not patients. Not customers. But shareholders.

Conventional medicine has to come back to profitability.  There are more direct ways to address these immune and inflammatory issues by existing means, which could be further developed, but they don’t sustain the pharma industry’s usual annual returns of 20-40% — a rate of stock profitability matched only by oil companies.

… On your pain.

If you have something to say about that, you can contact your political representatives here: http://www.usa.gov/Contact/Elected.shtml

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