사멸세포에서의 metalloproteinase-9의 작용
Up-regulation of Matrix Metalloproteinase-9 in Smooth Muscle Cell Undergoing Death
배지에 tetracycline이 없으면 사멸하는 평활근세포 (FADD-SMC)를 이용하여 metalloproteinase (MMP)와 사멸세포의 상관관계를 조사하였다. FADD-SMC를 tetracycline이 없는 배지에서 배양하는 경우 핵이 조각으로 잘라졌고 인산화한 p38과 ERK가 증가하고 MMP-9의 발현과 활성이 증가한 반면, cyclin D와 cyclin D의 발현은 감소하였다. 그리고 죽는 FADD-SMC에서 MMP-9의 발현은 immunofluorescen로 재확인하였다. MMP-9의 증가는 MAPK 억제제인 PD098059와 p38 MAPK 억제제인 SB203S80에 의하여 감소하였다. 그리고 MMP 억제제인 BB94는 FADD-SMC의 사멸을 감소시켰다.
This study investigated whether matrix metalloproteinases (MMPs) can be modified in apoptotic smooth muscle cell (SMC) using the SMC that undergoes apoptotic death by expressing Fas-associated death domain containing protein (FADD) when they are grown without tetracycline in culture medium. In the absence of tetracycline, FADD-SMC lost adherence and showed the fragmentation of the nuclei. In proportion to duration of tetracycline removal, phosphorylated form of p38 MAPK and of ERK increased, whereas phosphorylation of protein kinase B (PKB) was not changed very much in response to tetracycline The levels of cyclin A and cyclin D were also decreased in a time dependent manner. Up-regulation of MMP-9 expression and activity was observed when the SMC were grown without tetracycline. Immunoreactivity of MMP-9 was detected from both attached and floating FADD-SMCs grown without tetracycline. An inhibitor of MAPK kinase, PD098059, and an inhibitor of p38 MAPK, SB203580, inhibited the up-regulation of MMP-9. Treatment of the SMC with a synthetic MMP inhibitor, BB94, attenuated death occurring in the absence of tetracycline. These results indicate that SMC undergoing death is able to up-regulate MMP-9 and that the enzyme can affect cell viability.
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