While MG132 induced activation of caspase 12, 8, and Bak, mitochondrial cytochrome c release and subsequent activation of caspase cascade including caspase 9, 3, and 7, and Flupirtine destruction were totally abrogated in J/Bcl xL cells overexpressing Bcl xL, the ER strain mediated upregulation of Grp78/BiP and CHOP/GADD153 amounts, and activation of JNK and p38MAPK seemed to be sustained or reasonably increased. This proposed that among the MG132 induced apoptotic activities mediated via ER pressure, the activation of caspase 12 and 8 was sensitive to anti apoptotic role of Bcl xL as was the activation of mitochondria dependent caspase cascade. Furthermore, these results indicated that MG132 induced activation of mitochondriadependent caspase stream, which may be blocked by Bcl xL, was crucial for the induced apoptosis. Although the presence of the pot caspase inhibitor z VAD fmk completely blocked MG132 caused sub G1 top and many apoptotic activities such as activation of caspase 3, 7, and 8, it didn’t completely block activation of caspase 9, particularly the creation of 35 kDa active caspase 9. The clear presence of z VAD fmk also didn’t curb MG132 caused JNK and p38MAPK service and Dcm reduction. Since the active JNK and Endosymbiotic theory p38MAPK could trigger mitochondrial cytochrome c release, and since the proteolytic cleavage of 47 kDa procaspase 9 within the apoptosome appears to yield generally 35/12 kDa active forms except the feedback cleavage of 47 kDa procaspase 9 by 20 kDa active caspase 3 does occur, it had been probably that MG132 caused mitochondrial cytochrome c release may be started by JNK and/ or p38MAPK rather than tBid produced from the caspase 8dependent cleavage of Bid. The idea that caspase 8 activation driven by 17 kDa active caspase 3 was a feedback amplification system selling mitochondrial cytochrome c release via the action of tBid turned more evident by our data showing that both the inhibition of caspase 9 activity by z LEHD fmk or the inhibition of caspase 3 activity by z DEVD fmk may completely purchaseAfatinib stop MG132 induced activation of caspase 8 in addition to generation of active caspase 3. While 37 kDa active caspase 9 was rarely detected at in the current presence of z LEHD fmk or z DEVD fmk, 35 kDa active caspase 9 was detected at a comparable degree to that of the MG132 treated control cells. Under these conditions, only 20 kDa active caspase 3 was produced without causing caspase7 initial and PARP degradation. These results also confirmed that the reciprocal activation of caspase 9 and 3 downstream of mitochondrial cytochrome c release, which may produce two kinds of active caspase 9 and 17 kDa active caspase 3, was critical for MG132 induced activation of caspase 8 and 7 and deterioration of PARP.