ARL2 in colorectal cancer cells to study the role in the detoxification of aldehydes

[yoxiwhy]

Normal physiological conditions or pathological conditions, aldehydes and ketones, such as acrylic aldehyde (acrolein), crotonaldehyde (crotonaldehyde), 4 - hydroxy-nonenal (4-HNE in) and malondialdehyde (malondiadehyde) , if many components, including proteins and nucleic acids in the cells in vivo accumulation of too much will cause damage. This damage will lead to gene mutation, chromosomal breakage, abnormal cell signaling pathways, serious damage will result in apoptosis or necrosis. Intracellular defense system of the class of toxic metabolites of oxidation or reduction. Human arginase, type II(ARL2) are a new member of the aldo-keto reductase superfamily, which have higher expression in the normal digestive tract, but the biological functions not know much about it.

 

The protein with high expression in primary liver cancer and lung cancer, indicating that ARL2 may be involved in tumorigenesis, development or affect tumor cell drug sensitivity. This study explores the role of ARL2 in colorectal cancer cells on the aldehydes detoxification.By two chemical synthesis for of ARL2 the small molecular double-stranded RNA, siRNA, the sourceARL2 expression in colorectal cancer cell lines HCT8 cells was reduced by 60% and 90%. Cell growth experiments, ARL2 in HCT8 cells, the expression decreased obviously lead to the slowing down of cell growth. ARL2 expression of waterLevel reduce the HCT8 of cells single-cell growth capacity and soft agar colony formation ability and control cells were significantly reduced. Cell toxicity experiments show that, ARL2 HCT8 cells express a lower level, so that the cells become more sensitive to the toxicity of propylene aldehyde (25μm).We used RKO cells and HCT8 cells derived from colorectal cancer cell lines were established the ARL2 stable expression up and down the cell model. Experimental studies have shown that the stability of the ARL2 expression levels change, resulting in the sensitivity of the cells to propylene aldehyde, crotonaldehyde, and 4 - hydroxy-nonenal, a significant change. ARL2 expression in the cell, not only can reduce the cytotoxicity and DNA damage caused by these aldehydes and ketones, can also reduce cell mutation rate caused by these compounds. On the contrary, ARL2 expression level decreased significantly increase the sensitivity of the cells to acrylic aldehyde, crotonaldehyde, and 4 - hydroxy nonenal.Our experimental results show that ARL2 can reduce cell damage caused by reactive aldehydes reveals ARL2 played an important role in cell protection, and further clarify ARL2 in tumor formation and in the course of other diseases The role provides important experimental evidence and theoretical basis.