scholarly journals Zebrafish model of human Zellweger syndrome reveals organ specific accumulation of distinct fatty acid species and widespread gene expression changes

2021 ◽  
Author(s):  
Shigeo Takashima ◽  
Shoko Takemoto ◽  
Kayoko Toyoshi ◽  
Akiko Ohba ◽  
Nobuyuki Shimozawa

ABSTRACTIn Zellweger syndrome (ZS), lack of peroxisome function causes physiological and developmental abnormalities in many organs such as the brain, liver, muscles, and kidneys, but little is known about the exact pathogenic mechanism. By disrupting the zebrafish pex2 gene, we established a disease model for ZS and found that it exhibits a pathological condition and metabolic failures similar to that of human patients. By comprehensive analysis of fatty acid profile, we found organ specific accumulation and reduction of distinct fatty acid species such as an accumulation of ultra-very-long-chain polyunsturated fatty acids (ultra-VLCPUFAs) in the brain of pex2 mutant fish. Transcriptome analysis using microarray also revealed mutant-specific gene expression changes that might lead to the symptom, which include reduction of crystallin, troponin, parvalbumin, and fatty acid metabolic genes. Our data indicated that the loss of peroxisome results in widespread metabolic and gene expression changes beyond the causative peroxisomal function. These results suggest the genetic and metabolic basis of the pathology of this devastating human disease.

2010 ◽  
Vol 61 (3) ◽  
pp. 275-285 ◽  
Author(s):  
Evita Rostoka ◽  
Sergejs Isajevs ◽  
Larisa Baumane ◽  
Aija Line ◽  
Karina Silina ◽  
...  

Effects of Lycopene, Indole-3-Carbinol, and Luteolin on Nitric Oxide Production and iNOS Expression are Organ-Specific in RatsNatural compounds are known to modify NO content in tissues; however, the biological activity of polyphenol-rich food often does not correspond to the effects of individual polyphenols on NO synthase activity. The aim of this study was to see how natural compounds luteolin, indole-3-carbinol, and lycopene modify NO production in rat tissues and change the expression of the iNOS gene and protein. Indole-3-carbinol produced multiple effects on the NO level; it significantly decreased NO concentration in blood, lungs, and skeletal muscles and increased it in the liver. Indole-3-carbinol enhanced lipopolyssaccharide (LPS)-induced NO production in all rat organs. It decreased iNOS gene expression in the brain cortex of animals that did not receive LPS and up-regulated it in the LPS-treated animals. Lycopene increased the iNOS gene transcription rate in the brain cortex of LPS-treated animals. Luteolin did not modify NO production in any organ of LPS-untreated rats, nor did it affect gene expression in the liver. In the brain it slightly decreased iNOS gene expression. Luteolin decreased NO production in the blood of LPS-treated animals and the number of iNOS-positive cells in these animals. Our results suggest that changes in tissue NO levels caused by natural compounds cannot be predicted from their effect on NOS expression or activity obtained in model systems. This stresses the importance of direct measurements of NO and NOS expression in animal tissues.


2018 ◽  
Vol 433 (2) ◽  
pp. 448-460 ◽  
Author(s):  
Birgit Lengerer ◽  
Julia Wunderer ◽  
Robert Pjeta ◽  
Giada Carta ◽  
Damian Kao ◽  
...  

Author(s):  
Mohammed Ali Amira ◽  
Omar Hendawy Amin

10-hydroxy-trans-2-decenoic acid (10H2DA), also known as royal jelly acid, is the main lipid component of RJ. It possesses anti-tumor, neurogenic, anti-inflammatory, antioxidant, bactericidal, nematocidal, and estrogen-like properties. A limited number of studies demonstrate the potentials of its main fatty acid, 10-H2DA, for alleviating anxiety and depressive-like behaviors as well as for enhancing neuronal functioning. However, the exact mechanism through which 10-H2DA produces its effect is not well-understood. This mini review gives examples of how 10H2DA might positively contribute to the treatment of psychiatric and neurological disorders. In addition, it surveys the available knowledge about the molecular mechanism through which it regulates transcriptional processes and gene expression in the brain.


Plant Direct ◽  
2020 ◽  
Vol 4 (7) ◽  
Author(s):  
Ashley E. Cannon ◽  
Chengshi Yan ◽  
David J. Burks ◽  
Xiaolan Rao ◽  
Rajeev K. Azad ◽  
...  

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2863-2863
Author(s):  
Ralf Kronenwett ◽  
Elena Diaz-Blanco ◽  
Thorsten Graef ◽  
Ulrich Steidl ◽  
Slawomir Kliszewski ◽  
...  

Abstract In this study, we examined gene expression profiles of immunomagnetically enriched CD34+ cells from bone marrow (BM) of 9 patients with untreated CML in chronic phase and from 8 healthy volunteers using Affymetrix GeneChips. Additionally, in 3 patients CD34+ from peripheral blood (PB) were compared with those from BM. Differential expression of 12 candidate genes was corroborated by quantitative real-time RT-PCR. Following hybridization of labelled cRNA to Affymetrix GeneChips covering 8793 genes we used the statistical scripting language “R” for data analysis. For normalization a method of variance stabilization transformations was used. To identify significantly differentially expressed genes we used the Significance Analysis of Microarrays (SAM) algorithm. The intraindividual comparison of CD34+ cells from BM and PB in CML showed no differentially expressed genes which is different to normal CD34+ cells which had distinct gene expression patterns comparing circulating and sedentary CD34+ cells (Steidl et al., Blood, 2002). Comparing malignant BM CD34+ cells from CML with normal BM CD34+ cells 792 genes were significantly differentially expressed (fold change: >1.3; q-value: <0.03). 735 genes had a higher and 57 genes a lower expression in CML. Gene expression patterns reflected BCR-ABL-induced functional alterations such as increased cell-cycle and proteasome activity as well as decreased apoptosis. Downregulation of several genes involved in DNA repair and detoxification in CML might be the basis for DNA instability and progression to blast crisis. An interesting finding was an upregulation of fetal hemoglobin (Hb) components such as Hb gamma A and G in leukemic progenitor cells whereas no difference in adult Hb expression was observed suggesting an induction of fetal Hb synthesis in CML. Looking at genes involved in stem cell maintenance we found an upregulation of GATA2 and a reduced expression of proteins from the Wnt signalling pathway suggesting an increased self-renewal of CML hematopoietic stem cells compared to the normal counterpart. Moreover, several genes playing a role in ubiquitin-dependent protein catabolism and in fatty acid biosynthesis such as fatty acid synthase (FAS) were stronger expressed in CML. The functional role of FAS for leukemic cell growth was assessed in cell culture experiments. Incubation of the leukemic cell line K562 with the FAS inhibitor cerulenin (10 μg/ml) for 3 days resulted in death of 99% of cells suggesting that survival of leukemic cells depends upon endogenous fatty acid synthesis. In an attempt to find a specific gene expression pattern associated with response to imatinib therapy we divided the patients included in this study into two groups: maximal reduction of BCR-ABL transcript level <3-log vs. >3-log (major molecular remission) during therapy. Comparing pretherapeutic gene expression profiles of both groups we could not identify a pattern predictive for major molecular response. In conclusion, malignant CD34+ cells in CML have a specific gene expression pattern which seems not to be predictive for response to imatinib therapy.


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