Science Question Regarding CF

[buggygurl321]

So I did a science fair project for my school, using corn seeds and turmeric. Now, in seeds, no matter which way you turn them, the roots will bend and grow downwards, a process called gravitropism. It is caused by a hormone called auxin (stored in the tips of the roots) which is activated by calcium moving freely in the roots. Now, I tested first to see if turmeric (placed in a solidifying agent and put on the roots after they had been rotated 90 degrees) would supress the calcium and thus block gravitropism, indicating that it was an ion channel blocker (which has been hypothesized in studies involving CF mice). It was. So I won first place and a tyco electronics award and went to the Regional fair. There, I tested to see how effective it was against a known blocker, Verapamil (a wasp venom) by doing the same process but with the venom added to half of the seeds. This too proved positive, and indicated that they were equally effective (though in different doses). I placed first out of everyone there (~300 kids) and am going to the International fair in Indianapolis in May. So here's my question: I've researched online and in guidebooks about CF, but I can't find anything that explains how the sodium/chloride inbalance causes the mucus or the rest of the symptoms. Also, I did read that calcium supresses the mutated CFTR protein. But the calcium is very small in comparison to the protein. How exactly does that work? I know that these will probably be asked in Indianapolis and I'd like to be as informed as possible. I will obviously cite anyone who helps as a referece. Thanks very much!

Katie, 15 w/cf

 

[Scarlett81]

sweetie- all I can say is I feel very stupid listening to you.<img src="i/expressions/face-icon-small-happy.gif" border="0">

Wow-you're a very smart cookie! Wish I could help you. I have actually wondered the same exact thing-I've had it explained to me in detail. And from the little I can remeber-the it's inmbalance of sodium/chloride that attaches onto the mucus which is what makes it so thick.
I believe that's why we're on pulmozyme and hypertonic saline-b/c those substances actually cut the cellular strand that attaches onto the mucus, making it thinner.
As far as on a genetic level-how the sodium chloride comes about-all that-can't help you. It's been explained to me and i just don't remember!

 

[Ender]

Ok here is my understanding of it all.

In the epiphilial cells lining the wall, there are these things called cilia (ya I'm starting off basic). These cilia are like brushes that sweep germs and stuff up to be coughed. Now in order for it to work, it is encassed in a thin layer of water like mucus...whereas on top of that is the thicker mucus that actually holds the germs and dust. So nothing actually touches that first thin layer, it is just there for cilia action.

Well I think with cf we don't have that fine first layer (hence why people say we don't make enough mucus). Our lungs get bogged down cause our cilia has no possible way to remove this stuff....

Hyptertonic saline is supposed to hydrate the airways...and kinda re-create this first layer to help in ciliary action. Pulmozyme cleaves the dna that is left behind...from dead white cells and old bacteria...cause that's what comprimises most of our phlegm.

Now why does this happen in our cells? I think it is just a simple matter of isotonic and hypertonic solutions. There is more salt trapped in the the cells of the lungs cause of the cftr being unable to transport it...so the water outside of the cells which is supposed to help the cilia go into balancing the salt content in the cells. That's what i think, anyways.

I'd be happy to hear other peoples ideas <img src="i/expressions/face-icon-small-smile.gif" border="0">

Kiel

 

[Kanake676]

The lack of/malfunction of the Cystic Fibrosis Transmembrane Regulator (CFTR) Protein from the epithelial tissue of a CFer is what causes our problems. Normally, the job of this protein is to transport salt from one side of an epithelial tissue to another. As the salt is moved across these membranes, water also goes with it to support homeostasis in the body. If the water did not travel with the salt, then the concentration of the salt would be greater on one side of the membrane than the other.

So, when the salt fails to travel accross the membrane due to the malfuction or lack of the CFTR protien, the water also fails to travel since there is no need to balance the salt concentration outside the membrane. The places we see the greatest symptoms of this are the lungs and the pancreas.

In the lungs, the mucus that would normally be thin is thicker due to lack of water infusion (caused ultimately by the lack of salt transport). In the pancreas, salt normally is secreted (and with it water) to create a medium to transport the pancreatic secretions throught the ducts. Without the salt, the medium is much thicker, and therefore many of the secretions we need to digest food don't travel to where they need to go.

I'll do some research on the calcium question, I know I've heard it explained, but can't remember the details enough to explain right now! Hope I helped with the other question though!

 

[Kanake676]

I'm sorry all that is in one paragraph, when I typed it I put breaks in but it didn't seem to make it to the post...

 

[Kanake676]

Oh, one more thing.

The salty sweat is also caused by the lack/malfuction of the CFTR protein. A lot of salt is produced in the sweat glands and travels with the sweat to the surface of our skin. Normally, CFTR proteins would line the sweat duct and remove a lot of the salt from the sweat and take it into the body. Since this does not happen in cfers, the salt remains, travels to the bodies surface, and makes our sweat saltier than average.

 

[Kanake676]

Okay, I think I found the info you were looking for.

<a target=_blank class=ftalternatingbarlinklarge href="http://www.cellbiology.yale.edu/cellbio/pdfs/m_caplan/2002_Egan_NatureMed.pdf">Article</a>

Basically, the most common mutation with CF is the Delta F508 mutation. In this mutation, the CFTR protein is not transported to the epithelial linings where it is needed, but stays in the Endoplasmic Reticulum (ER). The ER is responsible for making proteins in the body. Chaperone proteins are responsible for transporting the CFTR protein out of the ER and to the epithelial tissues of the body. They need calcium to operate effectively. So, very small amounts of calcium in the ER (they are talking in quantities of millimolar) kind of kick the chaperone proteins into gear and the CFTR protein is then carried to where it needs to go.

So the calcium doesn't actually inhibit the mutated gene, it helps to treat the symptoms.

 

[Ender]

wow that's awesome news....

It makes me happy. Most of the new treatments are for people who have the cftr expressed on the surface of their cells. However most of us don't.

Using something like Tumeric or um....that chemical in that article (just kinda browsed it) would allow the protien to reah the surface, whereas those new drugs would be able to work.

Futhermore, it also explains why curcumin didn't really have too much of an affect in in vivo. It doesn't correct the defect, it just allows the already defective protien to travel to the surface. However, that should have some sort of positive affect, cause usually the defects where there is the protien present are the most mild.

Some thoughts.
Kiel

 

[Scarlett81]

see i knew there were some smarty pants here!

 

[dyza]

try this site http://www.ornl.gov/sci/techresources/Human_Genome/posters/chromosome/cftr.shtml

Craig

 

[buggygurl321]

Thanks guys for all your help! I leave for Indianapolis (where the fair's being held) on May 7. Yay!
Thanks again!
Katie 15w/cf

 

[imondeck]

Good luck Katie!

 

[buggygurl321]

Thanks! By the way, so that I can cite you all, what are your last names, Christian, Tami, and Craig? I already have your's, Kiel, thanks to your profile, but everyone else's won't come up.

Thanks!!!!

Katie 15 w/cf