Death ligands and receptors Fas-FasL hepatitis, Cholestatic liver disease, NASH ↓HCC viral hepatitis, steatosis (hepatocytes) ↑ PBC, PSC (chlangiocytes) ↑ TNF-α Inc in: Alcohol, hepatitis, ischaemia-reperfusion injury Caspases Cysteine-dependent aspartate specific proteases Synthesized as zymogens and require activation by other caspases to function Initiator caspases: 7,8,9,10 Scaffolding functions Executioner (effector) Activate DNAse Bcl-2 family of proteins Regulate mitochondrial dysfunction during apoptosis Pro-apoptotic Bax, Bak, Bok, Bid, Bim, Bad, Bmf, Hrk, Noxa, PUMA Anti-apoptotic Bcl-xL, Bcl-w, Mcl-1, A1 Bcl-2, Effector cells Neutrophils Natural killer (NK) cells T cells: CTLs Can signal for death of a target cell indirectly via IFN / TNF apop Can signal for death of a target cell directly via Fas/FasL signalling apop OR secretion of perforin and granzymes while attached to target cell granzyme entry through PM or endosomes apop Activated macrophages Lysosomal pathway Proteases (eg LPM) leaking out of lysosomes can induce apoptosis Process can be triggered from death receptor signalling Implicated in:
Death ligands and receptors Fas-FasL hepatitis, Cholestatic liver disease, NASH ↓HCC ↑ viral hepatitis, steatosis (hepatocytes) ↑ PBC, PSC (chlangiocytes) TNF-α Inc in: Alcohol, hepatitis, ischaemia-reperfusion injury Caspases Cysteine-dependent aspartate specific proteases Synthesized as zymogens and require activation by other caspases to function Initiator caspases: 7,8,9,10 Scaffolding functions Executioner (effector) Activate DNAse Bcl-2 family of proteins Regulate mitochondrial dysfunction during apoptosis Pro-apoptotic Bax, Bak, Bok, Bid, Bim, Bad, Bmf, Hrk, Noxa, PUMA Anti-apoptotic Bcl-2, Bcl-xL, Bcl-w, Mcl-1, A1 Effector cells Neutrophils Natural killer (NK) cells T cells: CTLs Can signal for death of a target cell indirectly via IFN / TNF apop Can signal for death of a target cell directly via Fas/FasL signalling apop OR secretion of perforin and granzymes while attached to target cell granzyme entry through PM or endosomes apop Activated macrophages Lysosomal pathway Proteases (eg LPM) leaking out of lysosomes can induce apoptosis Process can be triggered from death receptor signalling Implicated in: