Liver X Receptors differentially modulate central myelin gene mRNA levels in a region-, age- and isoform-specific manner

Author(s):  
Ghjuvan’ Ghjacumu Shackleford ◽  
Julien Grenier ◽  
Walid Abi Habib ◽  
Charbel Massaad ◽  
Delphine Meffre
2015 ◽  
Vol 112 (24) ◽  
pp. 7587-7592 ◽  
Author(s):  
Delphine Meffre ◽  
Ghjuvan’Ghjacumu Shackleford ◽  
Mehdi Hichor ◽  
Victor Gorgievski ◽  
Eleni T. Tzavara ◽  
...  

The identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) α and β are nuclear receptors activated by oxysterols that originated from the oxidation of cholesterol. They are crucial for cholesterol homeostasis, a major lipid constituent of myelin sheaths that are formed by oligodendrocytes. However, the role of LXRs in myelin generation and maintenance is poorly understood. Here, we show that LXRs are involved in myelination and remyelination processes. LXRs and their ligands are present in oligodendrocytes. We found that mice invalidated for LXRs exhibit altered motor coordination and spatial learning, thinner myelin sheaths, and reduced myelin gene expression. Conversely, activation of LXRs by either 25-hydroxycholesterol or synthetic TO901317 stimulates myelin gene expression at the promoter, mRNA, and protein levels, directly implicating LXRα/β in the transcriptional control of myelin gene expression. Interestingly, activation of LXRs also promotes oligodendroglial cell maturation and remyelination after lysolecithin-induced demyelination of organotypic cerebellar slice cultures. Together, our findings represent a conceptual advance in the transcriptional control of myelin gene expression and strongly support a new role of LXRs as positive modulators in central (re)myelination processes.


2018 ◽  
Author(s):  
Sheba Jarvis ◽  
Lee Gethings ◽  
Raffaella Gadeleta ◽  
Emmanuelle Claude ◽  
Robert Winston ◽  
...  

2021 ◽  
pp. 104927
Author(s):  
Zhi Liang ◽  
Tanwei Gu ◽  
Jianjiao Wang ◽  
Jianglian She ◽  
Yuxiu Ye ◽  
...  

Author(s):  
Wanting Shao ◽  
Christina Kuhn ◽  
Doris Mayr ◽  
Nina Ditsch ◽  
Magdalena Kailuwait ◽  
...  

Abstract Purpose The aim of this study was to investigate the expression of liver X receptors α/β (LXR) in primary breast cancer (BC) tissues and to analyze its correlations with clinicopathological parameters including patient survival. Methods In a well-characterized cohort of 305 primary BC, subcellular distribution of LXR was evaluated by immunohistochemistry. Correlations with clinicopathological characteristics as well as with patient outcome were analyzed. Results LXR was frequently localized in both nuclei and cytoplasms of BC cells, with stronger staining in nuclei. Total and nuclear LXR expression was positively correlated with ER and PR status. Overall survival analysis demonstrated that cytoplasmic LXR was significantly correlated with poor survival and appeared as an independent marker of poor prognosis, in stage I but not in stage II–III tumors Conclusion Altogether, these data suggest that cytoplasmic LXR could be defined as a prognostic marker in early stage primary BC.


2010 ◽  
Vol 76 (7) ◽  
pp. 2155-2164 ◽  
Author(s):  
Sherri L. Henderson ◽  
Catherine E. Dandie ◽  
Cheryl L. Patten ◽  
Bernie J. Zebarth ◽  
David L. Burton ◽  
...  

ABSTRACT In agricultural cropping systems, crop residues are sources of organic carbon (C), an important factor influencing denitrification. The effects of red clover, soybean, and barley plant residues and of glucose on denitrifier abundance, denitrification gene mRNA levels, nitrous oxide (N2O) emissions, and denitrification rates were quantified in anoxic soil microcosms for 72 h. nosZ gene abundances and mRNA levels significantly increased in response to all organic carbon treatments over time. In contrast, the abundance and mRNA levels of Pseudomonas mandelii and closely related species (nirS P) increased only in glucose-amended soil: the nirS P guild abundance increased 5-fold over the 72-h incubation period (P < 0.001), while the mRNA level significantly increased more than 15-fold at 12 h (P < 0.001) and then subsequently decreased. The nosZ gene abundance was greater in plant residue-amended soil than in glucose-amended soil. Although plant residue carbon-to-nitrogen (C:N) ratios varied from 15:1 to 30:1, nosZ gene and mRNA levels were not significantly different among plant residue treatments, with an average of 3.5 � 107 gene copies and 6.9 � 107 transcripts g−1 dry soil. Cumulative N2O emissions and denitrification rates increased over 72 h in both glucose- and plant-tissue-C-treated soil. The nirS P and nosZ communities responded differently to glucose and plant residue amendments. However, the targeted denitrifier communities responded similarly to the different plant residues under the conditions tested despite changes in the quality of organic C and different C:N ratios.


2001 ◽  
Vol 169 (2) ◽  
pp. 281-290 ◽  
Author(s):  
ZW Fu ◽  
T Kubo ◽  
K Sugahara ◽  
T Noguchi ◽  
H Kato

We investigated the effects of vitamin A (VA) nutritional status on the levels of expression of retinoic acid (RA) receptor-beta (RARbeta) gene in the various tissues of Japanese quail. VA deficiency caused a significant decrease in the mRNA levels of brain, liver, heart, lung and kidney RARbeta2/beta4, whereas no change was observed in the level of testis RARbeta2 transcript. In contrast, reduction in the RARbeta1 transcript caused by VA depletion was observed only in the lung, remaining unchanged in the other tissues. The administration of RA to the VA-deficient quail rapidly induced the expression of RARbeta2/beta4 mRNAs in all the tissues examined, but RA increased the expression of RARbeta1 transcript in the liver, heart, lung and kidney at a lower magnitude. RA could not change the expression of the brain RARbeta1 transcript, while it induced the expression of the testis RARbeta1 mRNA in a temporal way. These results clearly indicate that VA nutritional status differently regulates the expression of RARbeta1 and RARbeta2/beta4 transcripts in a tissue-specific manner.


2013 ◽  
Vol 18 (1) ◽  
pp. 106-117 ◽  
Author(s):  
Simon W. Beaven ◽  
Aleksey Matveyenko ◽  
Kevin Wroblewski ◽  
Lily Chao ◽  
Damien Wilpitz ◽  
...  

Hepatology ◽  
2015 ◽  
Vol 62 (2) ◽  
pp. 615-626 ◽  
Author(s):  
Fiona O'Mahony ◽  
Kevin Wroblewski ◽  
Sheila M. O'Byrne ◽  
Hongfeng Jiang ◽  
Kara Clerkin ◽  
...  

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