However, the expression of Caspase-10
was found to be only 2.86 folds as compared with the normal control group.
Granzyme B, the prototype of serine proteases, promote cleavage and activate several caspases, including caspase-3, caspase-6, caspase-7, caspase-8, caspase-9, and caspase-10
Executioner caspases (caspase-3, caspase-6, and caspase-7) and upstream effector caspases (caspase-2, caspase-8, caspase-9, and caspase-10
) are well known as mediators in AD brains .
This process leads to activation of initiator caspase-8 or caspase-10
In this experimental setting, we used, in addition to a pan-caspase inhibitor (Z-VAD-FMK), inhibitors of CASP8 (Z-IETD-FMK), CASP9 (Z-LEHD-FMK), and caspase-10
(CASP10; Z-AEVD-FMK) (R&D Systems, Minneapolis, MN, USA).
As a caspase-8 and caspase-10
homolog, c-FLIPL has a conserved aspartic acid residue (Asp376).
Together with caspase-10
it belongs to the so-called initiator caspase group, and is important effector activation competent.
The extrinsic pathway is triggered when death ligands bind to their respective cell surface death receptors through recruitment of FAS-associated death domain (FADD) protein, procaspase-8 through the formation of a complex that induces cell death and activation of the caspases (caspase-8 and caspase-10
FasL expression was up-regulated by taiwanin A at both the transcriptional and translational levels, following the activation of caspase initiator caspase-10
and effector caspase-7.
To evaluate the involvement of caspases in PCL-induced cell death, five caspase inhibitors, z-DEVD-fmk (caspase-3 inhibitor), z-IETD-fmk (caspase-8 inhibitor), z-LEHD-fmk (caspase-9 inhibitor), z-AEVD-fmk (caspase-10
) and z-VAD-fmk (pan-caspase inhibitor) were applied.
In the extrinsic way, the apoptotic signal begins by the union of extra cellular ligands to the surface of cell receptors, resulting in a recruitment of the cytosolic adapter of proteins, that activates the caspase-8 or caspase-10
initiator, and subsequently, the caspases effectors -3, -7 and possibly -6.
The cells were incubated with z-DEVD-fmk (caspase-3 inhibitor, 20 [micro]mol/1), z-IETD-fmk (caspase-8 inhibitor, 20 [micro]mol/[1.sup.-1]), z- LEHD-fmk (caspase-9 inhibitor, 20 [micro]mol/1), z-AEVD-fmk (caspase-10
inhibitor, 20 [micro]mol/1) and z-VAD-fmk (pan-caspase inhibitor, 20 [micro]mol/1) for 1 h, and then treated with SFL for 24 h.