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- 저자 : Pantha, Pramod (검색결과 2 건)
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Perilipin 5 is a novel target of nuclear receptor LRH-1 to regulate hepatic triglycerides metabolism
( Rubee Pantha ),( Jae-ho Lee ),( Jae-hoon Bae ),( Eun Hee Koh ),( Minsang Shin ),( Dae-kyu Song ),( Seung-soon Im ) 생화학분자생물학회 2021 BMB Reports Vol.54 No.9
Liver receptor homolog-1 (LRH-1) has emerged as a regulator of hepatic glucose, bile acid, and mitochondrial metabolism. However, the functional mechanism underlying the effect of LRH-1 on lipid mobilization has not been addressed. This study investigated the regulatory function of LRH-1 in lipid metabolism in maintaining a normal liver physiological state during fasting. The Lrh-1<sup>f/f</sup> and LRH-1 liver-specific knockout (Lrh-1<sup>LKO</sup>) mice were either fed or fasted for 24 h, and the liver and serum were isolated. The livers were used for qPCR, western blot, and histological analysis. Primary hepatocytes were isolated for immunocytochemistry assessments of lipids. During fasting, the Lrh-1<sup>LKO</sup> mice showed increased accumulation of triglycerides in the liver compared to that in Lrh-1f/f mice. Interestingly, in the Lrh-1<sup>LKO</sup> liver, decreases in perilipin 5 (PLIN5) expression and genes involved inβ-oxidation were observed. In addition, the LRH-1 agonist dialauroylphosphatidylcholine also enhanced PLIN5 expression in human cultured HepG2 cells. To identify new target genes of LRH-1, these findings directed us to analyze the Plin5 promoter sequence, which revealed -1620/-1614 to be a putative binding site for LRH-1. This was confirmed by promoter activity and chromatin immunoprecipitation assays. Additionally, fasted Lrh-1<sup>f/f</sup> primary hepatocytes showed increased co-localization of PLIN5 in lipid droplets (LDs) compared to that in fasted Lrh-1<sup>LKO</sup> primary hepatocytes. Overall, these findings suggest that PLIN5 might be a novel target of LRH-1 to mobilize LDs, protect the liver from lipid overload, and manage the cellular needs during fasting. [BMB Reports 2021; 54(9): 476-481]
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Fan, Ligang,Wang, Guannan,Hu, Wei,Pantha, Pramod,Tran, Kieu-Nga,Zhang, Hua,An, Lizhe,Dassanayake, Maheshi,Qiu, Quan-Sheng Elsevier 2018 Vol. No.
<P><B>Abstract</B></P> <P>Seedling establishment in an extreme environment requires an integrated genomic and physiological response to survive multiple abiotic stresses. The extremophyte, <I>Haloxylon ammodendron</I> is a pioneer species capable of colonizing temperate desert sand dunes. We investigated the induced and basal transcriptomes in <I>H. ammodendron</I> under water-deficit stress during early seedling establishment. We find that not only drought-responsive genes, but multiple genes in pathways associated with salt, osmotic, cold, UV, and high-light stresses were induced, suggesting an altered regulatory stress response system. Additionally, <I>H. ammodendron</I> exhibited enhanced biotic stress tolerance by down-regulation of genes that were generally up-regulated during pathogen entry in susceptible plants. By comparing the <I>H. ammodendron</I> basal transcriptome to six closely related transcriptomes in Amaranthaceae, we detected enriched basal level transcripts in <I>H. ammodendron</I> that shows preadaptation to abiotic stress and pathogens. We found transcripts that were generally maintained at low levels and some induced only under abiotic stress in the stress-sensitive model, <I>Arabidopsis thaliana</I> to be highly expressed under basal conditions in the Amaranthaceae transcriptomes including <I>H. ammodendron</I>. <I>H. ammodendron</I> shows coordinated expression of genes that regulate stress tolerance and seedling development resource allocation to support survival against multiple stresses in a sand dune dominated temperate desert environment.</P> <P><B>Highlights</B></P> <P> <UL> <LI> We report the transcriptomic signals of <I>H. ammodendron</I> in response to drought that contribute to plant survival. </LI> <LI> We highlight the transcriptional and biological processes for the survival of <I>H. ammodendron</I> at early developmental stage. </LI> <LI> We find abundant orthologs in extremophytes that are rare in Arabidopsis. </LI> <LI> These orthologs provide novel candidates to discover networks naturally selected as adaptations to environmental stresses. </LI> </UL> </P>
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