Mitochondrial NAD(P)+-dependent malic enzyme attenuates the macrophage-like differentiation

• Main Authors: Haur-Shin Sheu, 許濠薪
• Other Authors: Guang-Yaw Liu
• Format: Others
• Language: zh-TW
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/54279524984146209975

碩士 === 中山醫學大學 === 微生物免疫研究所 === 103 === Malic enzyme (Mitochondrial NAD(P)+ -dependent malic enzyme；ME2）According to the early studied, ME2 is associated with cancer metabolism, but mechanisms involved in the induced differentiation of leukemia cells are still unknown. In process of differentiating HL-60 cells by using TPA., we found that HL60 overexpression of ME2 will reduce macrophage differentiation resulting cell attachment and generate filopodia, and not only inhibits NF-κB activation, TNF-α, IL1β, (IL 6) expression but also reduce the expression and secretion of MMP-9, even the macrophage cell surface antigen CD14 also decreased. Meanwhile, in process of TAP induced macrophage differentiation, we found increase of autophagy-related proteins. However, overexpressed ME2 would inhibit related proteins such as ATG5, ATG7, LC3II, Beclin 1, and mTOR, P70S6K and BCL-2 will rise. When HL-60 overexpressed of ME2 add Embonic acid not only recovery NF-κB activation, expression of TNF-α, IL1β, IL 6 and secretion of MMP-9, but also increase the expression of autophagy. ME2 attenuates differentiation. Meanwhile, shRNA of down-regulation overexpressed ME2 of HL60 also can see Embonic acid with a similarTherefore, ME2 can be a therapeutic target for leukemia