| Objective:The ubiquitin proteasome system is another protein degradation in eukaryotic organisms besides autophagy,it can be degraded by ubiquitin protein to maintain cell stability.UCH(ubiquitin carboxyterminal hydrolases),is a member of the UPS family,in recent years,studies have shown that there is a close relationship between the occurrence and development of UCH and some tumors.Our previous studies found that the expression of UCH-L3 was up regulated in acute myeloid leukemia cell HL-60 autophagic cell death,and gene expression was significantly decreased in patients with acute myeloid leukemia in peripheral blood,the purpose of this paper is based on the prophase to further study the relationship between UCH-L1 and UCH-L5 and autophagic cell death in leukemia cell,and the roles they played in the development and treatment of leukemia,and then deeper discusses the ubiquitin proteasome system and autophagy in the role of the development and treatment of leukemia,indicateing a new direction for the treatment of leukemia.Methods:1.Add autophagy inducer rapamycin and autophagy inhibitor into HL-60 cells,RT-PCR detected the expression level of UCH-L1,UCH-L5 and LC3?.2.Western-blot detected the protein expression level of UCH-L1,UCH-L5,LC3? after treated by rapamycin and 3-MA.3.Add cytarabine into acute leukemia cells HL-60,RT-PCR detected the expression level of UCH-L1,UCH-L5 and LC3?.4.Extract peripheral blood mononuclear cells from acute myeloid leukemia patients,RT-PCR detected the expression level of UCH-L1 and UCH-L5 of both primary group and remission group.Results:1.After rapamycin treatment,RT-PCR detection of LC3? in the gene level expression were up regulated,the expression of UCH-L5 and UCH-L1 were down regulated;after 3-MA treatment,the expression of UCH-L1 and UCH-L5 were up regulated,LC3? was down regulated,which has statistically significance(p<0.05).2.After treatment with rapamycin,the expression of LC3? in protein level were up regulated,the expression of UCH-L1 and UCH-L5 were down regulated after rapamycin treatment.After 3-MA treatment,and the expression of UCH-L1 and UCH-L5 were up-regulated,the expression of LC3? in protein level were down regulated,which has statistically significance(p<0.05).3.After treatment with cytosine arabinoside,the expression of UCH-L1 and LC3? was up-regulated,UCH-L5 was down regulated,which has statistically significance(p<0.05).4.Peripheral blood gene level detection showed that,the expression of UCH-L1 in the primary group compared to the control group was down-regulated,which has statistically significance(p<0.05).The expression of UCH-L1 in remission group was up-regulated compared to the primary group,which has statistically significance(p<0.05).The expression of UCH-L1 in remission group compared to the primary group was up-regulated,which has statistically significance(p<0.05).The expression of UCH-L5 in the primary group and remission group were down-regulated,which has statistically significance(p<0.01,p<0.05).The expression of UCH-L5 in remission group was up-regulated compared to the primary group,which has statistically significance(p<0.05).Conclusion:1.After inducted acute leukemia cell HL-60 autophagy,the expression of UCH-L1 and UCH-L5 in gene and protein levels were changed,indicating that both are involved in rapamycin induced autophagy process.2.After treated with cytosine arabinoside,the expression of LC3? was up regulated,indicating that autophagy is involved in the process of cytarabine arabinoside induced cell death in acute myeloid leukemia;the expression of UCH-L1 was up regulated,the expression of UCH-L5 was down regulated;the expression changes of UCH-L1 and UCH-L5,suggesting that both of them are involved in the process of cytarabine arabinoside induced cell death in acute myeloid leukemia.3.The expression of UCH-L1 and UCH-L5 in the primary group and remission group were found significant different,which means that UCH-L1 and UCH-L5 may be related to the occurrence and development of acute myeloid leukemia. |
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