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Huan Wang,Hongsheng Ouyang,Yaping Tian,Zhuang Liu,Xiaolei Han,Xingxing Liu,Guangyao Ran,Gangqi Wang,Daxin Pang,Xiaochun Tang 한국생물공학회 2014 Biotechnology and Bioprocess Engineering Vol.19 No.4
Nitroalkene derivatives of nitro-oleic acid(OA-NO2) regulate pluripotent cell signaling in vivo underphysiological and pathological conditions. Angiotensin IItype 1 receptor (AT1R) plays an important role in thecardiovascular system. In this study, OA-NO2 reduced theAT1R mRNA level, specifically in primary smooth musclecells, showing a 70% reduction in rat smooth muscle cells(RASMCs) and a 50% reduction in pig smooth musclecells (PASMCs). These effects were not observed in CHOcells, which highly express AT1R. The AT1R mRNA decayrate was unchanged after OA-NO2 compared with OAtreatment. Nitric oxide (NO) and peroxisome proliferatoractivatedreceptor gamma (PPARγ) did not alter thereduced effects of OA-NO2 on the AT1R mRNA level inSMCs. However, Sp1-mediated activation of the AT1Rpromoter was reduced in response to OA-NO2 in RASMCsbut not 293T cells. In addition, the nuclear factor-kappa B(NF-κB) pathway was involved in the OA-NO2-mediateddownregulation of AT1R transcription in SMCs. Takentogether, our results demonstrate that OA-NO2 specificallyinhibits AT1R mRNA expression in primary smooth musclecells via the NF-κB pathway.
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Chongli Xu,Yu Liu,Yuchen Gong,Xinping Duan,Xiaochun Tang,Mingjun Zhang,Daxin Pang,Liqing Yu,Hongwei Zhao,Hongsheng Ouyang 한국유전학회 2015 Genes & Genomics Vol.37 No.2
Although Niemann-Pick C1-Like 1 (NPC1L1)plays a key role in intestinal cholesterol absorption, regulatingcholesterol metabolism and maintaining cholesterolmetabolic homeostasis, the molecular mechanism ofNPC1L1 in lipid-metabolism disorders leading to liverdisease remains largely unknown. Previous studies haveshown that NPC1L1 is related with the development offatty liver. Therefore, we hypothesized that NPC1L1 playsan important role in lipid-metabolism disorders and liverdisease by affecting the transcription of certain genesinvolved in lipid synthesis. To further elucidate the functionof NPC1L1, especially in the liver, we used somaticcellnuclear transfer to establish transgenic pigs thatexpressed human NPC1L1 in their livers. We investigatedsuperoxide dismutase activities and the levels of free fattyacids and malondialdehyde, a biomarker of lipid peroxidation. Superoxide dismutase activities significantlydecreased, and free fatty acid and malondialdehyde levelssignificantly increased in the NPC1L1 transgenic pigs,indicating that the overexpression of NPC1L1 in the liverresulted in severe lipid peroxidation. Our findings suggestthat NPC1L1 plays an important role in lipid-metabolismdisorders and liver disease.
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