TTP

THROMBOTIC THROMBOCYTOPENIC PURPURA (HYPOTHESIS CONTINUES)

Here is the example of a metastatic mechanism going bad when it hits the right ADAM.  Remember that ADAM are made of 2 basic domains, one an integrin and one a metalloproteinase domain.  The Metalloproteinase enters the Flippase-floppase (or sometimes scramblase)-like structure and is destined to be rejected outside, the Integrin is sent inside the cell.
Metalloproteinases are sent outside and attack collagen-like molecules to open the way to cell migration and allow Metastatic processes to move forward.  However, the cell membranes have a collagen-like structure, too.  So potentially the released Metalloproteinases could attack the cell.  The cell is not stupid and knows what metalloproteinase it has put out.  So it shields itself with Inhibitors and Decoy receptors from that specific metalloproteinase and the cell goes about its migration.

2 conclusions:

1. Insufficient inhibitors and decoy receptors to Metalloproteinases (and others such as Hydroeicosatetraenoic Acid) will have devastating effects.  If genetically the inhibitors are insufficient, and metalloproteinases are expressed massively, and this happens at the endothelial cell, massive and extensive destruction of endothelial cells throughout the body happens, exposing collagen like structures of the blood vessel walls.  This of course trigger extensive activation of platelets and the Thrombosis of TTP-like syndrome.  So in TTP, it is the inhibitor that is lacking.  (ie Von Willebrand cleaving protease inhibitors have also been cited).  And plasmapheresis removes the the Metalloproteinases (and microbial Antigens/toxin when relevent), stopping the onslaught.

2.What is in the Integrin domain is critical, in ADAM-17, the integrin domain is occupied by TNF-alpha, converting enzyme (TACE) which will free and activate the devastating Tumor Necrosis Factor.  Released massively, TNF can not only induce Apoptosis like certain other Cyclins (interleukine and Interferon ), but also leads directly to NECROSIS.  A massive uncontrolled septic-like syndrome kills rats after infusion of TNF.

ADAM 10, the disintegrin there gives you Amyloid structures of Alzheimer's.  TO BE SHORT, PICK THE ADAM AND SEE THE CONSEQUENT DISEASE ON YOUR OWN!

ADAM! A FLIPPASE, FLOPPASE AND/OR A SCRAMBLASE-LIKE MOLECULE !

MORE INSIGHT IN THE SECOND LAW:  PLEASE READ

Authors: Rhonda M. Perciavalle, Joseph T. OpfermanSee Affiliations

Summary

BCL-2 molecules are regulators of programmed cell death Defects in this pathway contribute to human diseases. One family member, MCL-1, is unique because its expression is tightly regulated and it is essential for promoting the survival of a myriad of cellular lineages. Additionally, MCL-1 promotes the maintenance of normal mitochondrial morphology and energy production. Dissection of these functions revealed recently that they depend on separate mitochondrial sublocalizations. MCL-1's antiapoptotic activity is restricted to the outer mitochondrial membrane (OMM), whereas its function in mitochondrial physiology requires localization to the matrix. These findings provide an attractive model for how MCL-1's diverse functions may contribute to normal cell homeostasis and function. MCL-1 is highly amplified in human cancer, suggesting that these functions may contribute to malignant cell growth and evasion of apoptosis.

Keywords

apoptosis; MCL-1; homeostasis; mitochondrial function; cancer; development

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THIS IS A SUMMARY OF AN ARTICLE FROM "TRENDS IN CELL BIOLOGY".
FOR MORE INFORMATION, PLEASE GO TO THE SOURCE.
WE ARE TRACKING SUPPORTIVE MATERIAL THAT REENFORCES OUR ASSUMPTIONS!
OUR ASSUMPTIONS STILL ARE THAT MEDICATIONS THAT AFFECT THE ACTINIC SCAFFOLDING  (MICROTUBULE/MICROFILAMENT) BYPASS THE Bcl-2 RESISTANCE.
HOW MUCH AUTOPHAGY PLAYS INTO THIS IS STILL TO BE DETERMINED.  AUTOPHAGY IS MEANT TO BE FOR CANCER SURVIVAL GLOBALLY AS A RESPONSE TO STRESS ON THE CANCER CELL.  BUT THERE COMES A POINT WHEN IT IS DETRIMENTAL AND LEADS TO NON CASPASE CELL DEATH.  OTHERS HAVE CALLED THIS (RIGHT OR WRONGLY) "NECROSIS".