Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.1 (aspartate aminotransferase)
 21,665 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Long noncoding RNAs (lncRNAs) have been shown to be implicated in acetaminophen (APAP)-induced liver injury (AILI). We applied this study to investigate the role and functional mechanism of KCNQ1 overlapping transcript 1 (KCNQ1OT1) in AILI. The AILI model was established by APAP treatment in mice. The liver injury was preliminarily evaluated by ALT and AST activities via the detection kits. The quantitative real-time polymerase chain reaction (qRT-PCR) was exploited for detecting the expression of KCNQ1OT1, microRNA-122-5p (miR-122-5p), and carboxylesterase 2 (CES2). Protein levels were analyzed via Western blot. 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT) assay, and flow cytometry were separately applied to determine cell proliferation and apoptosis rate. Inflammation was assessed by enzyme-linked immunosorbent assay (ELISA). Dual-luciferase reporter assay was implemented to testify the intergenic combination. The function of KCNQ1OT1 in vivo was explored through KCNQ1OT1 knockdown in mice. APAP triggered the downregulation of KCNQ1OT1 and CES2 in mice serums. KCNQ1OT1 upregulation could relieve the AILI in HepaRG cells, which were abrogated by CES2 downregulation. KCNQ1OT1 served as a sponge of miR-122-5p and miR-122-5p directly targeted CES2. KCNQ1OT1 overexpression abated the AILI through the miR-122-5p/CES2 axis in HepaRG cells in vitro and mice in vivo. The collective results clarified that KCNQ1OT1 weakened the AILI in vitro and in vivo by the miR-122-5p/CES2 axis, providing an explicit molecular mechanism and selectable therapeutic strategy of AILI.
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PMID:LncRNA KCNQ1OT1 ameliorates the liver injury induced by acetaminophen through the regulation of miR-122-5p/CES2 axis. 3277 42

The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.
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PMID:Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo. 3282 27


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