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KLF10 inhibits CYP450 to reduce TAA-induced hepatic injury
Azra Memon,Yuri Seo,Joo-Yong Lee,Woon Kyu Lee 한국실험동물학회 2021 한국실험동물학회 학술발표대회 논문집 Vol.2021 No.7
Kruppel-Like Factor 10 (KLF10), an important transcription factor for hepatic glucose and lipid metabolism thought to be linked with liver injury and repair. However, it is not clear if KLF10 plays a role in reducing injury or activating repair in TAA-induced liver injury. Also, the molecular mechanism of KLF10 in the liver injury model is largely unknown. Here, we demonstrated that TAA-induced liver toxicity was significantly increased in KLF10 knockout mice. Strikingly, 70% of KLF10-/- mice die within 48 hours after TAA 300 mg/kg/BW treatment that generally known as a safe dose to induce liver injury without notable lethality. Histological analysis of TAA-treated liver of KLF10 knockout mice revealed a significant increase of TUNNEL positive shrunk hepatic nuclei, characteristics of pyknosis, inflammation, and massive hemorrhage. Also, biochemical analysis revealed KLF10 knockout mouse experienced a significant amount of oxidative stresses after TAA treatment evidenced by the increase of malondialdehyde, a well-known oxidative stresses marker, and the decrease of glutathione, the most abundant cellular thiol antioxidant, in TAA-treated KLF10-/- mouse correlated with an increased protein level of iNOS. For the mechanistic understanding of the protective role of KLF10 against TAA-induced liver toxicity, we showed KLF10 negatively regulates CYP450, a key enzyme to convert nontoxic TAA into toxic metabolites TAASO and TASO2 that triggers necrosis and liver injury. Our findings suggested a protective role of KLF10 against TAA-induced liver injury and provided a unique angle to understand the liver injury.
Characterization of the porcine Nanog 5’-flanking region
Azra Memon,Ki-Duk Song,Woon-Kyu Lee 아세아·태평양축산학회 2018 Animal Bioscience Vol.31 No.3
Objective: Nanog, a homeodomain protein, has been investigated in humans and mice using embryonic stem cells (ESCs). Because of the limited availability of ESCs, few studies have reported the function and role of Nanog in porcine ESCs. Therefore, in this study, we investigated the location of the porcine Nanog chromosome and its basal promoter activity, which might have potential applications in development of ESCs specific marker as well as understanding its operating systems in the porcine. Methods: To characterize the porcine Nanog promoter, the 5'-flanking region of Nanog was isolated from cells of mini-pig ears. BLAST database search showed that there are two porcine Nanog genomic loci, chromosome 1 and 5, both of which contain an exon with a start codon. Deletion mutants from the 5'-flanking region of both loci were measured using the Dual-Luciferase Reporter Assay System, and a fluorescence marker, green fluorescence protein. Results: Promoter activity was detected in the sequences of chromosome 5, but not in those of chromosome 1. We identified the sequences from –99 to +194 that possessed promoter activity and contained transcription factor binding sites from deletion fragment analysis. Among the transcription factor binding sites, a Sp1 was found to play a crucial role in basal promoter activity, and point mutation of this site abolished its activity, confirming its role in promoter activity. Furthermore, gel shift analysis and chromatin immunoprecipitation analysis confirmed that Sp1 transcription factor binds to the Sp1 binding site in the porcine Nanog promoter. Taken together, these results show that Sp1 transcription factor is an essential element for porcine Nanog basal activity the same as in human and mouse. Conclusion: We showed that the porcine Nanog gene is located on porcine chromosome 5 and its basal transcriptional activity is controlled by Sp1 transcription factor.
Azra Memon,Yuliya Pyao,Yerin Jung,Hwa-Sik Choi,송기덕,이운규 한국유전학회 2021 Genes & Genomics Vol.43 No.4
Background Krüppel–like factor 10 (KLF10) belongs to the Sp1-like transcription factor family, which plays an important role in many directions, e.g., cell proliferation, apoptosis, and diferentiation. Its 5′ upstream regions are conserved across mammalian species. However, the regulatory mechanism has not been elucidated yet. Objective Nonetheless the basal transcriptional regulation mechanisms of these regions are unknown. Here, we characterized it which is indispensable for the basal transcription of the Klf10 gene. Methods Seven deletions of 5′ upstream DNA fragments from the 10 kb mKlf10 genomic DNA were produced by PCR and cloned into the upstream of the luciferase (Luc) reporter gene in the pGL3 basic plasmid. Result The luciferase reporter assay showed that the DNA sequence at positions from −101 to +68 was required for a principle activity in the promoter of mKlf10 gene, in which transcriptional factor binding motifs, one JunB and two Sp1 sites, are included. Mutations at the sequence of JunB motif, but not at the two Sp1, abrogated the promoter activity completely, suggesting the indispensable role of JunB site for basal transcription of mKlf10 gene. Moreover, electrophoretic mobility and supershift assays (EMSA) uncovered that JunB protein bound to this region specifcally. Conclusion Taken together, our study revealed that the JunB but not Sp1 at mKlf10 promoter functions as a positive basic factor for the transcriptional activity of the gene.
WHEN SHAKESPEARE TRAVELS ALONG THE SILK ROAD: TARDID, AN IRANIAN ADAPTATION OF HAMLET
GHANDEHARION, AZRA,JAGHRAGH, BEHNAZ HEYDARI,SABBGH, MAHMOOD GHORBAN Academia Via Serica 2017 Acta Via Serica Vol.2 No.1
Media has become an inseparable companion of $21^{st}$ century culture, exerting immense influence on our daily lives. This article aims to reveal how cultural aspects and media in a particular part of the Silk Road have adapted Western cannons. Iran has redefined and transformed Western culture through the modern Silk Road by the method of cinematic adaptation. Karim-Masihi employs the general plot of Hamlet, the well-known drama by William Shakespeare (1564-1616), in his movie Tardid (Doubt 2009); however, he transforms some of the characters to reflect the current socio-cultural aspects of Iranian society. One of the characters is named Siavash, whose life is similar to Hamlet. In passivity, he awaits his imminent death and other tragic consequences. Yet, the movie ends differently. It is not an Elizabethan tragedy in a strict sense, although the final scenes abound with corpses. This article aims to find the similarities and differences between the two works, while reasoning the significance of the alterations. It concludes with how different cultures react to the same themes.
As Rumi Travels along the Silk Road in Feminist Costume: Shafak's The Forty Rules of Love
GHANDEHARION, AZRA,KHAJAVIAN, FATEMEH Academia Via Serica 2019 Acta Via Serica Vol.4 No.1
Transnational exchange has been an inseparable part of both the ancient and modern Silk Road. This paper shows how Rumi (1207-1273), a famous Persian Sufi poet, travels along the Silk Road in the $21^{st}$ century. With the birth of a Rumi phenomenon in the West, Silk Road artists have rediscovered and adapted him for different purposes. Elif Shafak, the Turkish-British novelist and women's rights activist, espouses feminist beliefs in her bestseller, The Forty Rules of Love (2010). Benefiting from the views of feminist theorists like Woolf, de Beauvoir and Friedan, this paper reveals how Shafak appropriates Rumi for her feminist purposes. Forty Rules of Love's protagonist, Ella Rubinstein is analyzed, compared and contrasted with her former literary counterparts Pinhan and Zeliha, heroines of Shafak's previous novels. By adapting Rumi's definition of equality, Shafak shows how egalitarianism must pervade the relationship between women and men. The adaptation of Rumi's ideas regarding the equality of sexes finds a different dimension when Shafak reveals that all humanity possesses femininity and masculinity at the same time. By means of ideas prevalent in the ancient Silk Road, the five classical elements theory, and the yin and yang principle, Shafak portrays unity within contradictions. It is concluded that although individuals might belong to different typologies of the five symbolic elements of nature, they can at the same time complement one another's inharmonious personalities peacefully. The process of integration of female and male sexes can be expedited by opening up one's heart to a universal love.