The induction of dog CYP3A12 and CYP3A26 mRNA levels was evaluated in liver slices after treatment with 22 xenobiotics. Eleven of the 22 xenobiotics increased 3A12 mRNA by more than four-fold, while nine did the same for 3A26 mRNA. A four-fold increase in the mRNA level was used as the cut-off for indication of induction based on the noise level of the real time-PCR. A good correlation was found between the mRNA levels for 3A12 and 3A26 after treatment with compounds, suggesting that these two CYPs may be co-induced. Induction of CYP3A4 in human hepatocytes was evaluated after treatment with the same 22 compounds. Thirteen out of the 22 compounds increased the 3A4 mRNA levels by more than four-fold. When the mRNA levels of 3A4 and 3A12 were compared after treatment with compounds, no correlation was found. The regulation of CYP3A expression has been demonstrated to be controlled by pregnane X receptor (PXR). Upon examination of the sequence homology and the three-dimensional structures of human PXR and a dog PXR model, only two different amino acids (met323/val and arg410/lys) were found in the ligand-binding domain. This finding suggests that these two amino acids may play a role in the binding specificity of ligands.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.2174/187231209787176399 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Novel insights into the interaction between IGF2BPs and ncRNAs in cancers.
Cancer Cell Int
December 2024
Department of General Surgery, Affiliated Zhongda Hospital of Southeast University, Nanjing, 210009, China.
Insulin-like growth factor II mRNA-binding proteins (IGF2BPs), a family of RNA-binding proteins, are pivotal in regulating RNA dynamics, encompassing processes such as localization, metabolism, stability, and translation through the formation of ribonucleoprotein complexes. First identified in 1999 for their affinity to insulin-like growth factor II mRNA, IGF2BPs have been implicated in promoting tumor malignancy behaviors, including proliferation, metastasis, and the maintenance of stemness, which are associated with unfavorable outcomes in various cancers. Additionally, non-coding RNAs (ncRNAs), particularly long non-coding RNAs, circular RNAs, and microRNAs, play critical roles in cancer progression through intricate protein-RNA interactions.
View Article and Find Full Text PDFIdentification of the arachidonic acid 5-lipoxygenase and its function in the immunity of Apostichopus japonicus.
Fish Shellfish Immunol
December 2024
Department of Biotechnology, School of Biological Engineering, Dalian Polytechnic University, Dalian 116034, Liaoning Province, P. R. China; Dalian Jinshiwan Laboratory, Dalian, China. Electronic address:
A number of studies have been demonstrated that arachidonate 5-lipoxygenase (ALOX-5) plays a role in regulating a range of physiological and pathological processes through the catalysis of leukotriene formation from arachidonic acid (ARA). The coding sequence of ALOX-5 from Apostichopus japonicus (Aj-ALOX-5) was successfully amplified, resulting in a 2028 bp ORF sequence that encodes 674 amino acids. A comparison of the amino acid sequence with those of other 5-lipoxygenases revealed that Aj-ALOX-5 has the N-terminal "PLAT domain" and C-terminal "lipoxygenase structural domain" characteristic of this enzyme family.
View Article and Find Full Text PDFNAT10 drives endometriosis progression through acetylation and stabilization of TGFB1 mRNA.
Mol Cell Endocrinol
December 2024
International Peace Maternity & Child Health Hospital, Shanghai Municipal Key Clinical Speciality, Institute of Embryo-Fetal Original Adult Disease, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China. Electronic address:
Endometriosis, a gynecological disorder marked by pelvic pain and infertility, has its pathogenesis and pathophysiology significantly influenced by epigenetics, as these factors have been well characterized. However, the role of RNA-mediated epigenetic regulation in endometriosis remains to be elucidated. In our study, we found that N4-acetylcytidine (acC) RNA modification and N-acetyltransferase 10 (NAT10) were significantly upregulated in endometrial lesions compared to eutopic endometrium.
View Article and Find Full Text PDFLoss-of-function SLC25A20 mutation causes carnitine-acylcarnitine translocase deficiency by reducing SLC25A20 protein stability.
Gene
December 2024
Department of Medical Genetics/Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China; Guangdong Provincial Key Laboratory of Single Cell Technology and Application, Guangzhou 510515, China; Department of Fetal Medicine and Prenatal Diagnosis, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address:
Background/aim: Autosomal-recessive carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of long-chain fatty acid oxidation caused by variants in the SLC25A20 gene. Under fasting conditions, most newborns with severe CACTD experience sudden cardiac arrest and hypotonia, often leading to premature death due to rapid disease progression. Understanding of genetic factors and pathogenic mechanisms in CACTD is essential for its diagnosis, treatment, and prevention.
View Article and Find Full Text PDFLncRNA TMC3-AS1 silence alleviates lipopolysaccharide-induced acute kidney injury by suppressing Wnt5a-mediated autophagy and pyroptosis pathway.
Mol Cell Probes
December 2024
Department of Nephrology, The Second Affiliated Hospital of Harbin Medical University, Harbin 150086, China. Electronic address:
Long non-coding RNA TMC3-AS1 is identified to be upregulated by lipopolysaccharide (LPS) in inflammatory disease, but its role in acute kidney injury (AKI) is almost unknown. The study investigated the involvement of TMC3-AS1 in LPS-induced AKI and its downstream molecular regulatory mechanism. Our data suggested that knocking down TMC3-AS1 significantly reduced renal dysfunction, tissue inflammation and tissue damage in LPS-induced mice, and promoted cell viability, inhibited inflammation, apoptosis and necrosis in LPS-stimulated human renal tubular epithelial cells HK2.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!