Worksheet 12-18 - The professor\'s name was Pascale Charest. PDF

Preview

Summary

The professor's name was Pascale Charest....

Description

Dana Woods Pascale Charest BIOC 568 19 April 2018 Worksheet 12-18

Niloofar Ghadirian Presentation

Targeted apoptosis of myofibroblasts with the BH3 mimetic ABT-263 reverses established fibrosis

1. What is apoptosis? What is the difference between the intrinsic and extrinsic pathway? Apoptosis, also known as controlled cell death, is a naturally occurring process that kills cells. This process happens during normal growth and development, such as when the webbing between your fingers goes away while you are still in the womb. It also protects the cells, as this process is triggered whenever there is damage to the cell that is unable to be repaired. There are two apoptotic pathways: the intrinsic pathway and the extrinsic pathway. The intrinsic pathway is in response to DNA damage or excessive stress to the cell. This activates p53, which allows for release of cytochrome c from the mitochondria to initiate caspase involvement. The extrinsic pathway involves Fas receptors that become activated in response to an external Fas ligand. This causes several downstream caspases to be activated. The main difference between the two pathways is that the intrinsic pathway starts from within the cell and the extrinsic pathway starts from outside the cell. 2. What is the main finding of this paper? The authors found that a certain BH3 mimetic drug (ABT-263) inhibit BCLXL proteins. These proteins normally bind to BH3-only proteins such as BIM to keep them sequestered from the mitochondrial membrane. This sequestration inhibits apoptosis, as these BH3-only proteins are required for release of cytochrome c from the mitochondria. With the drug present, the BCL-XL proteins will bind to it instead, leaving BIM free to allow for adequate mitochondrial priming for apoptosis. The authors observed that this mechanism of action allowed for reversal of established fibrosis due to the myofibroblasts present, and concluded that this drug would be a great candidate as a treatment option for several fibrotic diseases....