Analysis of regulatory mechanism for liver regeneration by various types of cell death(autophagy and apoptosis)

为了研究自噬和p62/SQSTM 1在脂肪肝再生中的调节作用，我们研究了肝/肝细胞中的脂肪变性细胞死亡（自噬和凋亡）。(1)细胞/肝组织自噬评价方法的建立。本研究通过LC 3和p62/SQSTM 1的表达及电镜观察，定量评价细胞和肝组织的自噬情况。(2)我们研究了p62/SQSTM 1表达的调控机制及其与凋亡/自噬和氧化应激的关系。p62/SQSTM 1的表达受自噬的特异性调控，但不受凋亡的调控，也受PI3-K/PDK/Akt依赖性信号的正调控。p62/SQSTM 1还参与抑制细胞氧化应激和损伤。在小鼠肝脏中，p62/SQSTM 1通过Nrf-2增加细胞抗氧化分子如SOD、Ref-1和过氧化氢酶，并抑制氧化应激。

In order to examine the regulatory role of autophagy and p62/SQSTM1 in fatty liver regeneration, we studied steatotic cell death (autophagy and apoptosis) in liver/hepatocytes.(1) Establishment of evaluation method for autophagy in cell/liver tissue. We tried to quantitatively evaluate autophagy of cells and liver tissue by expressions of LC3 and p62/SQSTM1, and electron micrograph.(2) We studied the regulatory mechanism of p62/SQSTM1 expression and its relation to apoptosis/autophagy and oxidative stress. p62/SQSTM1 expression was regulated by autophagy specifically, not by apoptosis, but also regulated positively by PI3-K/PDK/Akt-dependent signals. p62/SQSTM1 was also involved in suppression of cellular oxidative stress and injury. In mouse liver, p62/SQSTM1 increased cellular anti-oxidative molecules such as SOD, Ref-1 and Catalase through Nrf-2 and suppressed oxidative stress.