Fine-tuning cell organelle dynamics during mitosis by small GTPases / 医学前沿

During mitosis, the allocation of genetic material concurs with organelle transformation and distribution. The coordination of genetic material inheritance with organelle dynamics directs accurate mitotic progression, cell fate determination, and organismal homeostasis. Small GTPases belonging to the Ras superfamily regulate various cell organelles during division. Being the key regulators of membrane dynamics, the dysregulation of small GTPases is widely associated with cell organelle disruption in neoplastic and non-neoplastic diseases, such as cancer and Alzheimer's disease. Recent discoveries shed light on the molecular properties of small GTPases as sophisticated modulators of a remarkably complex and perfect adaptors for rapid structure reformation. This review collects current knowledge on small GTPases in the regulation of cell organelles during mitosis and highlights the mediator role of small GTPase in transducing cell cycle signaling to organelle dynamics during mitosis.

Role of transient receptor potential cation channel subfamily M member 2 in hepatic ischemia-reperfusion injury in the mouse and the underlying mechanisms / 中南大学学报(医学版)

OBJECTIVES@#To investigate the role of transient receptor potential cation channel subfamily M member 2 (TRPM2) in hepatic ischemia-reperfusion injury of mouse (HIRI) and the possible mechanisms.@*METHODS@#Sixty adult male C57BL/6 mice were randomly divided into 4 groups: a sham group (S group), a HIRI model group (M group), a TRPM2 adenovirus interference vector group (T group), and a TRPM2 adenovirus control vector group (C group) (=15 in each group). The liver tissues of mice before perfusion were obtained. The efficiency of adenovirus infection was detected by fluorescence microscopy, and the silencing efficiency of adenovirus against TRPM2 was detected by real-time PCR.The abdominal aorta blood and liver tissues were collected from mice at 2, 4 and 8 h after reperfusion. The activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum of mice were detected. Hepatic pathological changes were examined by hematoxylin-eosin (HE) staining. The protein expression of TRPM2 and Rac family small GTPase 1 (RAC1) in liver tissues was detected by Western blotting. Changes of malondialdehyde (MDA), superoxide dismutase (SOD) and myeloperoxidase (MPO) activities in liver tissues were detected by enzyme-linked immunosorbent assay.@*RESULTS@#A strong signal of green fluorescence was observed in the liver tissues of mice in the T and C groups compared to the S or M group. Compared with the S, M or C group, the expression of TRPM2 mRNA in liver tissue in the T group was significantly down-regulated (all <0.05). The morphology of hepatocytes was normal in the S group under light microscope.Hepatic sinus dilatation, congestion, hepatocyte degeneration, central necrosis of lobule, and massive inflammatory granulocyte infiltration were observed in the M and C group, respectively. The degree of hepatocyte damage in the T group was significantly reduced compared with that in the M and C group, respectively. Compared with the S group, the serum ALT and AST activities in the M, T and C groups were significantly increased at 2, 4 and 8 h after reperfusion (all <0.05). Compared with the M or C group, the serum ALT and AST activities in the T group were significantly lower in serum of mice at 2, 4, and 8 h after reperfusion (all <0.05). Compared with the M or C group, the serum SOD activity in the T group was significantly increased at 2, 4, and 8 h after reperfusion (all <0.05), while the serum MDA and MPO activities were significantly decreased (all <0.05). The protein expression of TRPM2 and RAC1 in liver tissues in the T group were significantly lower than those in the M and C groups at 2, 4 and 8 h after reperfusion (all <0.05).@*CONCLUSIONS@#Pretreatment with TRPM2 adenovirus interference vector can effectively silence TRPM2 gene expression in liver tissues of mice and attenuate HIRI, which may be related to inhibiting oxidative stress and reducing the expression of RAC1 protein.

Correlation between δ-catenin and Cdc42 expression in non-small cell lung cancer / 中国癌症杂志

Background and purpose:δ-catenin is a member of the p120 catenin subfamily, which can directly bind to E-cadherin on the cell membrane, forming E-cadherin/catenin complex. δ-catenin can also affect the cytoskeleton assembly by regulating the activity of Cdc42 (Small GTPase). Therefore, this study detected the expression of δ-catenin and Cdc42 in non-small cell lung cancer (NSCLC) and investigated the relationship between them.Methods:The expressions of δ-catenin and Cdc42 in 122 cases of NSCLC were detected by immunohistochem-istry. This study also used Western blot and real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR) to detect the protein and mRNA expressions of δ-catenin and Cdc42 in lung cancer tissues. After up-regulating or down-regulating δ-catenin in lung cancer cell line, the activity of Cdc42 and invasion ability of lung cancer cells were detect-ed by G-LISA and Transwell.Results:The mRNA and protein expression of δ-catenin and Cdc42 in lung cancer tissues was signiifcantly higher than that in normal lung tissues. In 122 NSCLC cases, the δ-catenin positive expression rate was 65.57% (80/122), and the Cdc42 overexpression rate was 68.03% (83/122). There was a good correlation betweenδ-catenin positive expression and Cdc42 overexpression (P<0.001). The co-expression of δ-catenin and Cdc42 was related to the high clinical stage, poor differentiation, adenocarcinoma and lymph node metastasis of lung cancer (P<0.05), and was signiifcantly associated with poor prognosis in patients with lung cancer. In the lung cancer cell line, the expression and the activity of Cdc42 were changed by regulating the δ-catenin expression, which affected invasion ability of the lung cancer cells.Conclusion:The δ-catenin expression was significantly correlated with the Cdc42 expression. The co-expression of δ-catenin and Cdc42 in lung cancer was correlated with the poor prognosis of lung cancer.