Programmed cell Death سخنران : آقای محسن نجاری کارشناس ارشدآزمایشگاه انگل شناسی بیمارستان قائم ( عج )

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Presentation transcript:

Programmed cell Death سخنران : آقای محسن نجاری کارشناس ارشدآزمایشگاه انگل شناسی بیمارستان قائم ( عج )

Programmed cell Death Apoptosis)) Mohsen Najari Msc In Medical Parasitology

Programmed cell Death مرگ برنامه ریزی شده یا ( آپپتوز ) مکانیسمی است که بوسیله آن سلولهای غیر طبیعی وبا عملکرد معیوب توسط سیستم ایمنی شناخته و حذ ف می گردند. مرگ برنامه ریزی شده یا ( آپپتوز ) مکانیسمی است که بوسیله آن سلولهای غیر طبیعی وبا عملکرد معیوب توسط سیستم ایمنی شناخته و حذ ف می گردند.

Apoptosis Apoptosis (type I PCD) is an irreversible, efficient mechanism to remove undesired cells within hours while preventing initiation of the inflammatory pathway Apoptosis (type I PCD) is an irreversible, efficient mechanism to remove undesired cells within hours while preventing initiation of the inflammatory pathway

Apoptosis In metazoa, it is initiated by extrinsic stimuli activating the death receptor of the tumour necrosis factor receptor (TNFR) family (which includes TNF-R1, TNF-R2 and the Fas receptor) In metazoa, it is initiated by extrinsic stimuli activating the death receptor of the tumour necrosis factor receptor (TNFR) family (which includes TNF-R1, TNF-R2 and the Fas receptor)

Apoptosis or by the intrinsic stress-induced mitochondrial pathway, that is, through the action of the tumour-suppressing protein p53 or by the intrinsic stress-induced mitochondrial pathway, that is, through the action of the tumour-suppressing protein p53

Apoptosis Lack of survival signals, such as growth factors, also leads to apoptosis. Lack of survival signals, such as growth factors, also leads to apoptosis.

Apoptosis. Triggering of the apoptotic pathway is tightly controlled in mammalian cells by a balance between pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) members of the Bcl- 2 family.. Triggering of the apoptotic pathway is tightly controlled in mammalian cells by a balance between pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) members of the Bcl- 2 family.

Apoptosis The hallmark and point of no return of apoptosis is the activation of the caspase- mediated proteolytic cascade The hallmark and point of no return of apoptosis is the activation of the caspase- mediated proteolytic cascade

Apoptosis The extrinsic and the intrinsic way both lead to the processing and thereby to the activation of initiator caspases (caspase-8 and -9) The extrinsic and the intrinsic way both lead to the processing and thereby to the activation of initiator caspases (caspase-8 and -9)

Apoptosis The initiator caspases activate the effector caspases (caspase-3, -6 and -7), which in turn execute apoptosis by cleavage of many substrates. The initiator caspases activate the effector caspases (caspase-3, -6 and -7), which in turn execute apoptosis by cleavage of many substrates.

Apoptosis Apoptosis-induced release of cytochrome c from mitochondria is due to increased permeability of the outer mitochondrial membrane. Apoptosis-induced release of cytochrome c from mitochondria is due to increased permeability of the outer mitochondrial membrane.

Apoptosis Together with Apaf-1 and caspase-9, released cytochrome c forms a protein complex known as an apoptosome. Together with Apaf-1 and caspase-9, released cytochrome c forms a protein complex known as an apoptosome.

Apoptosis The apoptosome leads to the activation of caspase-9 and, subsequently, the activation effector caspases The apoptosome leads to the activation of caspase-9 and, subsequently, the activation effector caspases

Mechanism of Apoptosis Please see a video clip on apoptosis for clearance of topic, celebrated from : Please see a video clip on apoptosis for clearance of topic, celebrated from : Apoptosis_iPod.mp4.gz Apoptosis_iPod.mp4.gz Apoptosis_iPod.mp4.gz Melbourn medical university Astralia Melbourn medical university Astralia

Inhibition of Apoptosis

Effective molecule death-inducing signaling complex (DISC) death-inducing signaling complex (DISC) Fas-associated protein with death domain (FADD) Fas-associated protein with death domain (FADD) death effector domain (DED) death effector domain (DED) apoptosis-activating factor (Apaf)-1 apoptosis-activating factor (Apaf)-1 inhibitor of apoptosis proteins (IAPs), inhibitor of apoptosis proteins (IAPs), of phosphatidylserine( PS) of phosphatidylserine( PS) heat shock proteins (HSP70), (Hsp90) heat shock proteins (HSP70), (Hsp90) NF-kB-mediated inhibition of apoptosis NF-kB-mediated inhibition of apoptosis c-FLIP (I-Flice, Cash, Casper), a specific inhibitor of Caspase 8 c-FLIP (I-Flice, Cash, Casper), a specific inhibitor of Caspase 8

Applications of inhibitor molecule in Apoptotic path way سلولهای سرطانی به طور عموم سلولهای سرطانی به طور عموم کلیه ارگانیسم های مهاجم داخل سلولی کلیه ارگانیسم های مهاجم داخل سلولی انگلها انگلها باکتریها باکتریها ویروس ها ویروس ها

این عوامل به منظور زنده ماند ن و ادامه بقاء اقدام به فعال نمودن مکانیسم های آنتی آپپتوز می نمایند. این عوامل به منظور زنده ماند ن و ادامه بقاء اقدام به فعال نمودن مکانیسم های آنتی آپپتوز می نمایند. آنتی آپپتوز آنتی آپپتوز زنده ماندن انگل های لشمانیا در درون ماکروفاژها از این مکانیسم تبعیت می کند. زنده ماندن انگل های لشمانیا در درون ماکروفاژها از این مکانیسم تبعیت می کند.

سایر عوامل انگلی بلاستوسیستیس هومینیس بلاستوسیستیس هومینیس مالاریا ( در مرحله کبدی ) مالاریا ( در مرحله کبدی ) تریکوموناواژینالیس تریکوموناواژینالیس توکسوپلاسما گوندی توکسوپلاسما گوندی تریپانوزوم کروزی ( در عضله قلب ) تریپانوزوم کروزی ( در عضله قلب ) از مکانیزم مهار آپپتوز برای ادامه حیات انگلی در میزبانان خود استفاده می کنند. از مکانیزم مهار آپپتوز برای ادامه حیات انگلی در میزبانان خود استفاده می کنند.