Apoptosis and venetoclax
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- Опубликовано: 28 авг 2018
- Animation by Etsuko Uno, Walter and Eliza Hall Institute
www.wehi.edu.au/wehi-tv
This animation is in two parts.
Part 1: Apoptosis is a type of cell death that removes diseased and unwanted cells from the body. This part of the animation illustrates how apoptotic molecules are released from the mitochondria, an organelle inside the cell. It focuses on proteins that interact on the surface of the mitochondria to release apoptotic molecules. This release of proteins from the mitochondria is considered a point of no return and is therefore a critical step in the cell death process.
Part 2: The anti-cancer drug, venetoclax, works by forcing susceptible cells to undergo apoptosis. More: www.wehi.edu.au/research-rese... 
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This is really interesting and amazingly illustrated!
thanks to these kind of animations, we're able to understand the mechanisms of molecules and not only go blindly through it..
Whoever named apoptosis and venetoclax is/are way cooler than whoever named the Extremely Large Telescope
The people at your institute are amazing for creating this miracle drug!! A million thank you’s!!!
it's prob another big company that made venetoclax
@@DihydrogenMonoxideGuy Genentech Abbvie (Roche)
Wonderful, so amazing to look inside a person like this.
You guys are good. Keep doing these. Until I understand everything about everything.
1:21 CHOMP!
I don't kmow how many time I view this video. Very beauty , I love.
Awesome video, great commentary!
Y'all should get to networking, you could get tens of thousands of views with the right sharing
most stupid comment ;)
it should be more popular.
I hope venetoclax can see the difference between cancer cells and normal cells
yes the video mentioned it was selective, but didn't illustrate how.
Analogy: think of it this way: you have a cancer cell that wants to die but cannot, so in this case a car that wants to drive off of a cliff. The gas pedal is down, but the emergency brake is pulled so the car goes nowhere. Venetoclax takes out the brake, so the car can drive over the cliff, the cancer cell can die. Normal cells in this analogy would be a car parked at the cliff enjoying the view, it doesn't matter whether the brake is off or on because the car doesn't have the gas on.
A bit more biological explanation: Venetoclax will affect all cells that have the 'guardian' proteins, because venetoclax inhibits the guardian proteins, but it selectively kills cancer cells. How does this happen? Well, the difference between cancer cells and normal cells is that cancer cells are constantly trying to die by turning on the initiator and pore-forming proteins, whereas normal cells are not. Cancer cells are very sick but continue to live because they have an abundance of guardian proteins keeping them alive. So when venetoclax is used normal cells live, because they don't want to die, and cancer cells die, because they do want to die.
but don't normal cells get caught in the crossfire? i mean, guardian receptors exist in normal cells too - their natural role seems to be as a safety device to counteract accidental triggerings. Venetoclax will disable this safety ability in normal cells, so while you're on it then your normal cells will get accidentally triggered into Apoptosis at a greater rate.
I guess it's ok as long as accidental Apoptosis triggers are rare (you can probably afford to lose a healthy cell here and there), and as long as you're not on Venetoclax for too long. Right?
This seems to fit the Chemotherapy's reputation of injecting your system with poisons that will basically kill all of your cells - but kills cancer cells faster.
It seems to be sortof like if an army's guns were all faulty and wouldn't fire, because of an issue with the gun's safety mechanism, so to solve it they just disabled ALL the guns safety mechanisms for a month or so. During those few months everyone's guns work so the army can fight it's enemies, but because of the lack of safety mechanism they also do have a much greater rate of unfortunate friendly fire incidents. It's still preferred to having non-functional guns tho, coz that'd kill the whole army within days.
Very good thinking. Well you are essentially correct, Venetoclax will effect every cell that has the guardian protein that it takes out. What the video doesn't illustrate (because, I assume is outside the scope of the simple mechanism) is that there are multiple different guardian proteins with the main ones being named Bcl-2, Bcl-XL, Bcl-2, Mcl-1 and A1. Venetoclax only takes out Bcl-2. Some cancers rely exclusively on Bcl-2 to live, so by taking it out they die, while most normal cells don't because they have the other guardian proteins to protect the cell.
It is a numbers game, ill be using easy numbers to illustrate my point but it is in no means an accurate number. Say a normal cell has 100 guardian proteins, 20 of each of the 5 above. So in this case 20 Bcl-2. this normal cell may "accidentially" turn on the apoptosis mechanism by making 30 initiator BH3-proteins. The cell lives because it is 30 initiator versus 100 guardian. Veneoclax is used and takes out all the Bcl-2. The normal cell still lives because it is 30 initiator proteins to 80 guardian proteins.
In the case of the cancer cell that relies on Bcl-2, the cancer cell has either shifted the proportion of Bcl-2 such that it is 80 Bcl-2 to 20 of the otherguardian proteins OR the cancer cell has increased the number of Bcl-2 (both at the same time is likely). So lets say the cancer cell has 300 guardian proteins, with 200 of them being Bcl-2. This cancer cell has also increased the amount of initiator proteins because it is actively trying to die by triggering apoptosis, so say 250 initiator proteins. The cancer cell lives because it is 250 initiator versus 300 guardian. Venetoclax takes out all of the Bcl-2, the cell now dies because it is 250 initiator proteins versus 100 guardian proteins.
Venetoclax is VERY different than classical chemotherpy. Classical chemo is non-specific affecting all cells but rapidly dividing cells (like cancer, hair, bone marrow etc) the most, whereas venetoclax is a very targeted drug, taking out only the Bcl-2 guardian protein and cancer for the reasons explained above.
@@chimerathirteen7057 Thank you
I start venetoclax next week… I’m sure this visual and the sound effects will be playing in my brain! Die guardian proteins!!☠️Apoptosis to the rescue!💪💪
This is amazing
Awesome video
Greetings from Bulgaria 🤗
Why every molecule is in constant vibratory motion even when they are not interacting with each other? What is the significance of this constant motion?
Heat (thermal energy). Molecules are constantly in motion, colliding with each other and bouncing back and forth.
@@WEHImovies thank you for answering my question...very thought provoking video
@@puspitasaha3412 Brownian movement is an example
Other molecules that would be present are not shown/invisible for simplicity's sake and for the audience to see what they're (only) supposed to see.
Interesting that killing the cell is the job of an originally foreign cell.
I assume it was originally a predation mechanism.
Did it work ?
ionnis, y u do dis
woww wowwwww
Crazy
Can anyone explain to me in Arabic
الجزء الاول عن الاستموات
آلية انتحار موجودة في كل خلايا الجسم يتم تفعيلها عند تعب الخلية او فقدانها لفعاليتها
المتقدرة(ميتاكوندريا) تلعب دور اساسي في هذه العملية حيث يوجد على غشائها بروتين مثل baxيقوم بتفعيل الانتحار حيث عند تفعيله يتجمع و يثقب غشاء المتقدرة فيتسرب بروتين السيتكروم الذي يقوم بتشكيل جسيم الاستموات و تفعيل طلائع الكاسبيز فيقوم شلال الكاسبيزات بكسر بروتينات الخلية و تدميرها
ولكن هناك بروتينات اخرى مثل bcl2 تعطل بروتين bax و تمنعه من قتل الخلية طالما تقوم بعملها كما يجب
و بروتينات تقوم بمراقبة حالة الخلية مترصدة اي خلل لتبدأ عندها بتفعيل bax و الارتباط مع bcl2 وتعطيله وبالتالي تفعيل لاستموات و الوصول لنقطة ال لاعودة
.
الجزء الثاني venetoclax
السرطان خلايا خالدة غير فاعلة حيث تتكاثر بشكل دائم و هي غير قادرة على تفعيل الاستموات رغم رغبتها بذلك حيث اصاباها خلل ف بعض لانواع تصنع كميات كبيرة من bcl2 و هي كميات تبقي السرطان حيا و بالتالي الخلية السرطانية لا تموت
دواء venetoclax للسرطان
تم السماح باستخدامه ل سرطان الدم اللمفاوي الخبيث
يقوم الدواء بمهاجمة بروتين bcl2 و تعطيله و بالتالي السماح للخلية السرطانية بتفعيل الاستموات و انتحارها
So that’s why kids never do drugs
Thanks too much it is the most expensive gift of universe thanks ❤️
this is the most horrific thing i have ever seen.