scholarly journals Comparison of gene expression of metallothioneins, ubiquitin and p53 in fibroblasts from lung and skin of rats of different age

2015 ◽  
Vol 6 (2) ◽  
pp. 161-164 ◽  
Author(s):  
Y. G. Kot ◽  
E. V. Kot ◽  
E. S. Morosova ◽  
E. E. Persky ◽  
M. A. Gritsenko ◽  
...  

We studied gene expression of five metallothioneins (MT 1-5), ubiquitin and protein p53 and their products in fibroblasts culture of the skin and lungs of white rats of different ages (2 weeks, 1, 3, and 24 months) and determined its (metallothionein 1-5 types, ubiquitin, p53) product quantity. All these proteins are protective ones, but perform their functions by using different mechanisms. Metallothionein bind, transport and excrete ions of bivalent metals, ubiquitin controls the cleavage of the defective and short-lived proteins in the proteasome, protein p53 controls apoptosis, thus ensuring the genome stability. The similarity of age dynamics of gene expression of ubiquitin and MT of cells of both sources has been shown – maximum at 3 months. Expression of p53 gene has a difference: both in the skin and lungs expression increases up to 24 months. Product quantity of p53 has a minimum in the skin at 3 months and remains constant; in the lungs, this value has a maximum at 1 month.


2008 ◽  
Vol 37 (1) ◽  
pp. 87-92
Author(s):  
E. Nádasi ◽  
I. Prantner ◽  
T. Dávid ◽  
I. Ember


2021 ◽  
Vol 22 (14) ◽  
pp. 7624
Author(s):  
Mohammad Saeed ◽  
Alejandro Ibáñez-Costa ◽  
Alejandra María Patiño-Trives ◽  
Laura Muñoz-Barrera ◽  
Eduardo Collantes Estévez ◽  
...  

Objectives: This study employed genetic and functional analyses using OASIS meta-analysis of multiple existing GWAS and gene-expression datasets to identify novel SLE genes. Methods: Four hundred and ten genes were mapped using SNIPPER to 30 SLE GWAS loci and investigated for expression in three SLE GEO-datasets and the Cordoba GSE50395-dataset. Blood eQTL for significant SNPs in SLE loci and STRING for functional pathways of differentially expressed genes were used. Confirmatory qPCR on SLE monocytes was performed. The entire 12p11 locus was investigated for genetic association using two additional GWAS. Expression of 150 genes at this locus was assessed. Based on this significance, qPCRs for DNM1L and KRAS were performed. Results: Fifty genes were differentially expressed in at least two SLE GEO-datasets, with all probes directionally aligned. DDX11, an RNA helicase involved in genome stability, was downregulated in both GEO and Cordoba datasets. The most significant SNP, rs3741869 in OASIS locus 12p11.21, containing DDX11, was a cis-eQTL regulating DDX11 expression. DDX11 was found repressed. The entire 12p11 locus showed three association peaks. Gene expression in GEO datasets identified DNM1L and KRAS, besides DDX11. Confirmatory qPCR validated DNM1L as an SLE susceptibility gene. DDX11, DNM1L and KRAS interact with each other and multiple known SLE genes including STAT1/STAT4 and major components of IFN-dependent gene expression, and are responsible for signal transduction of cytokines, hormones, and growth-factors, deregulation of which is involved in SLE-development. Conclusion: A genomic convergence approach with OASIS analysis of multiple GWAS and expression datasets identified DDX11 and DNM1L as novel SLE-genes, the expression of which is altered in monocytes from SLE patients. This study lays the foundation for understanding the pathogenic involvement of DDX11 and DNM1L in SLE by identifying them using a systems-biology approach, while the 12p11 locus harboring these genes was previously missed by four independent GWAS.



1999 ◽  
Vol 276 (4) ◽  
pp. C946-C954 ◽  
Author(s):  
Li Li ◽  
Ji Li ◽  
Jaladanki N. Rao ◽  
Minglin Li ◽  
Barbara L. Bass ◽  
...  

The nuclear phosphoprotein p53 acts as a transcription factor and is involved in growth inhibition and apoptosis. The present study was designed to examine the effect of decreasing cellular polyamines on p53 gene expression and apoptosis in small intestinal epithelial (IEC-6) cells. Cells were grown in DMEM containing 5% dialyzed fetal bovine serum in the presence or absence of α-difluoromethylornithine (DFMO), a specific inhibitor of polyamine biosynthesis, for 4, 6, and 12 days. The cellular polyamines putrescine, spermidine, and spermine in DFMO-treated cells decreased dramatically at 4 days and remained depleted thereafter. Polyamine depletion by DFMO was accompanied by a significant increase in expression of the p53 gene. The p53 mRNA levels increased 4 days after exposure to DFMO, and the maximum increases occurred at 6 and 12 days after exposure. Increased levels of p53 mRNA in DFMO-treated cells were paralleled by increases in p53 protein. Polyamines given together with DFMO completely prevented increased expression of the p53 gene. Increased expression of the p53 gene in DFMO-treated cells was associated with a significant increase in G1 phase growth arrest. In contrast, no features of programmmed cell death were identified after polyamine depletion: no internucleosomal DNA fragmentation was observed, and no morphological features of apoptosis were evident in cells exposed to DFMO for 4, 6, and 12 days. These results indicate that 1) decreasing cellular polyamines increases expression of the p53 gene and 2) activation of p53 gene expression after polyamine depletion does not induce apoptosis in intestinal crypt cells. These findings suggest that increased expression of the p53 gene may play an important role in growth inhibition caused by polyamine depletion.



Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 834
Author(s):  
Ekaterina Blinova ◽  
Dmitry Pakhomov ◽  
Denis Shimanovsky ◽  
Marina Kilmyashkina ◽  
Yan Mazov ◽  
...  

Background: The main goal of our study was to explore the wound-healing property of a novel cerium-containing N-acethyl-6-aminohexanoate acid compound and determine key molecular targets of the compound mode of action in diabetic animals. Methods: Cerium N-acetyl-6-aminohexanoate (laboratory name LHT-8-17) as a 10 mg/mL aquatic spray was used as wound experimental topical therapy. LHT-8-17 toxicity was assessed in human skin epidermal cell culture using (4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A linear wound was reproduced in 18 outbred white rats with streptozotocin-induced (60 mg/kg i.p.) diabetes; planar cutaneous defect was modelled in 60 C57Bl6 mice with streptozotocin-induced (200 mg/kg i.p.) diabetes and 90 diabetic db/db mice. Firmness of the forming scar was assessed mechanically. Skin defect covering was histologically evaluated on days 5, 10, 15, and 20. Tissue TNF-α, IL-1β and IL-10 levels were determined by quantitative ELISA. Oxidative stress activity was detected by Fe-induced chemiluminescence. Ki-67 expression and CD34 cell positivity were assessed using immunohistochemistry. FGFR3 gene expression was detected by real-time PCR. LHT-8-17 anti-microbial potency was assessed in wound tissues contaminated by MRSA. Results: LHT-8-17 4 mg twice daily accelerated linear and planar wound healing in animals with type 1 and type 2 diabetes. The formulated topical application depressed tissue TNF-α, IL-1β, and oxidative reaction activity along with sustaining both the IL-10 concentration and antioxidant capacity. LHT-8-17 induced Ki-67 positivity of fibroblasts and pro-keratinocytes, upregulated FGFR3 gene expression, and increased tissue vascularization. The formulation possessed anti-microbial properties. Conclusions: The obtained results allow us to consider the formulation as a promising pharmacological agent for diabetic wound topical treatment.



Author(s):  
J. Bourhis ◽  
J. Bosq ◽  
G.D. Wilson ◽  
B. Bressac ◽  
P. Wibault ◽  
...  


2001 ◽  
Vol 34 (5) ◽  
pp. 415-420 ◽  
Author(s):  
George J Soleas ◽  
David M Goldberg ◽  
Linda Grass ◽  
Michael Levesque ◽  
Eleftherios P Diamandis


2005 ◽  
Vol 11 (2) ◽  
pp. 123-127
Author(s):  
Wang Cheng-xin ◽  
Huang Xuan ◽  
Zhao Xiao-ling ◽  
Deng Hao


1992 ◽  
Vol 87 (suppl 4) ◽  
pp. 71-73 ◽  
Author(s):  
Manami Tanaka ◽  
Tadashi Matsu-Ura ◽  
Hirohisa Hirai




2018 ◽  
Vol 16 ◽  
pp. 88-95 ◽  
Author(s):  
Eman A.E. Badr ◽  
Mohamed Farag Ali Assar ◽  
Suzy F. Gohar ◽  
Mohamed Hamdy Badr ◽  
Rawda Magdy Hathout ◽  
...  


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