Methylglyoxal (MGO) is predominantly produced as a by-product of the glycolysis pathway. The glyoxalase system effectively removes it in a healthy organism. However, this process is impaired, and MGO ...level is elevated in people with diabetes. MGO's effects on proliferation were mostly studied in cancer cells, and the data in other cell types are limited. This study inspected the proliferative capacity of MGO in vascular smooth muscle cells (VSMCs), which have a crucial role in atherosclerosis and restenosis. The roles of ERK1/2 MAPK and Akt phosphorylations in proliferation were determined. Telmisartan, irbesartan, and NF-κB inhibitor JSH-23's roles in protecting the cells from MGO-induced proliferation were also investigated. Primary VSMCs were isolated from the rat aorta. The proliferation was spectrophotometrically measured by using a tetrazolium salt (Wst-1). The cells were cultured in standard media (SM, glucose conc. 5.5 mM) or high glucose media (HGM, glucose conc. 25 mM; an in vitro model of hyperglycemia). ERK1/2 MAPK and Akt phosphorylations were determined by the western blot method. MGO triggered the proliferation at 24, 48, and 72 hrs in SM and 48 and 72 hrs in HGM. Low doses of MGO such as 1-10 µM can induce proliferation. The phosphorylated ERK1/2 MAPK and Akt participated in MGO-induced proliferation. Telmisartan, irbesartan, and JSH-23 effectively alleviated the proliferation and Akt phosphorylation. MGO could proliferate VSMCs even at low doses. Moreover, hypertensive diabetic patients might benefit from a sartan family drug to protect VSMCs from MGO-induced proliferation.
The term 'multiculturalism' has been widely quoted to explain and study transnational networks and cultural changes on a global scale. This book focuses on the application of multicultural theories ...and perspectives in the field of literature and particularly in contemporary narratives. Bringing together ten studies which blur the limits of conventional discourse, and employing an interdisciplinary approach to address research problems using methods and insights borrowed from multiple disciplines, it features theoretical and analytical writings on multiculturalism and its traces in literatures that subvert the essentialist binary frameworks of ethnicity, race, nation and identity in a variety of texts. These include Martin Amis's The Pregnant Widow, Kazuo Ishiguro's The Remains of the Day, Salman Rushdie's Midnights Children and Shame, Hanif Kureishi's Something to Tell You, J. G. Ballard's High-Rise, Lady Annie Brassey's Sunshine and Storm in the East; or, Cruises to Cyprus and Constantinople, and Sir Henry Blount's A Voyage into the Levant. Approaching theoretical issues concerning multiculturalism from multiple perspectives and looking for its traces in different time periods and genres, this book will be of interest for scholars and researchers working in the fields of literature and cultural studies, as well as students studying in the same fields and the general reader.
Presenting the outlines of the postmodern philosophy of historiography as it shapes the theoretical background for the analysis of the historical novel, this study aims to render that the recent ...understanding of history and its reconceptualization in decolonizing fictional (re)writings still provides the “re-visionary” stance seen in contemporary postcolonial narratives. After the introduction of postmodern innovations in theoretical and imaginative writing, there has emerged a rather
newfangled
view of the historical novel and an increasing inclination for narratives that attempt to reimagine historical moments and chronicles they integrate into their fictional worlds to pursue a re-visionary questioning. The critical frameworks of postcolonial historical fiction and speaking subalterns have moved on in postmillennial historical novels and political novels. Considering that postcolonial literary theories and fictional (re)writings attempt to deconstruct homogenous discourses and the Eurocentric (history) writing of the colonizer, it is claimed that, for the sake of textual decolonization, recent works of postcolonial historical writing intersect in several ways with the
newfangled
view of the historical novel.
William Golding’s 1959 Free Fall depicts the narrator/character Samuel Montjoy’s retrospective interrogation of his past in his “non-chronological” autobiography to understand his present self. His ...first-person narration is a journey into his memories presented according to their importance for him at different stages of his life (the narrated self) and shows the role of memory in shaping the present self (the narrating self). The narrator regulates his memories to conceive a coherent pattern in his autobiographical account which will also give meaning to his life and help construct a unified identity. However, he adopts a structure that has to rely on his remembering/forgetting, which problematizes the idea of constructing the self through unreliable memory. With this quality of the novel as an early example of the “fiction of memory,” Golding’s text is inventive and looks forward to contemporary narrative approaches to autobiographical writing. Free Fall has been widely studied as an existentialist novel due to the novelist’s questioning the concepts of freedom to choose and fall through the protagonist’s quest for self-knowledge. However, the aim of this study is to analyse Golding’s work as autobiografiction and trauma narrative where the text presents an account of the protagonist’s attempt for reconstructing the self through memories subject to his modifications and offers the therapeutic use of his self-narration.
William Golding’s 1959 Free Fall depicts the narrator/character Samuel Montjoy’s retrospective interrogation of his past in his “non-chronological” autobiography to understand his present self. His ...first-person narration is a journey into his memories presented according to their importance for him at different stages of his life (the narrated self) and shows the role of memory in shaping the present self (the narrating self). The narrator regulates his memories to conceive a coherent pattern in his autobiographical account which will also give meaning to his life and help construct a unified identity. However, he adopts a structure that has to rely on his remembering/forgetting, which problematizes the idea of constructing the self through unreliable memory. With this quality of the novel as an early example of the “fiction of memory,” Golding’s text is inventive and looks forward to contemporary narrative approaches to autobiographical writing. Free Fall has been widely studied as an existentialist novel due to the novelist’s questioning the concepts of freedom to choose and fall through the protagonist’s quest for self-knowledge. However, the aim of this study is to analyse Golding’s work as autobiografiction and trauma narrative where the text presents an account of the protagonist’s attempt for reconstructing the self through memories subject to his modifications and offers the therapeutic use of his self-narration.
İngiliz romancı William Golding’in 1959 yılında basılan ve Türkçeye ancak 2019’da Serbest Düşüş başlığı ile çevrilen eseri, roman başkişisi ve anlatıcısı Samuel Montjoy’un kronolojiyi takip etmeden ...kaleme aldığı otobiyografisi üzerinden sürdürdüğü geçmişini irdelemesiyle ortaya çıkan kişilik sorgulamasını ve kişiliğini yeniden şekillendirme çabasını konu edinir. Montjoy’un anlatısı, anılarına bir yolculuk, dolayısıyla geçmişte nasıl biri olduğunu ve şimdiki kişiliğini hangi geçmiş olayların şekillendirdiğini anlama serüveni olarak sunulur. Anlatıcı ve otobiyografi yazarı rollerini üstlenen Montjoy, anılarını okuyucusu ve daha önemlisi kendisi için “tutarlı” kabul edilebilecek bir örüntü içerisinde vermeye çabalarken bu çabasının aynı zamanda tutarlı bir kişilik oluşturmak için de olduğunu anlarız. Otobiyografisinde yer verdiği anıları, hayatının farklı evrelerinde kendisi için önem sırasına göre okuyucusuna aktarılır. Bu sayede anlatıcı, kişilik arayışında hatırlama/unutmanın önemine dolaylı da olsa işaret etmiş olur. Hatırlama/unutmaya dayalı bir yapı içerisinde anılarını ele aldığı ve hayat hikayesini okuyucusuna da aynı biçimde aktardığı için ancak zihnimizin ve hatıralarımızın aldatmacaları ile sürekli yeniden yazılan bir benlik oluşturabileceğimiz gerçeğini de ortaya çıkarır. Bu özelliği ile roman, otobiyografi yazımı alanında günümüz anlatı kuramlarına yaklaşmaktadır. Golding’in Serbest Düşüş romanı özgür irade, seçim yapma ve insanın düşüşü gibi konuları ele aldığı için daha çok varoluşçu romanlarla birlikte ve onların kuramsal çerçevesi dahilinde irdelenmiştir. Ancak Golding’in bu romanını otobiyografi yazımı ve kurgusal otobiyografi oluşturma çerçevesinde değerlendiren bu çalışma, roman başkişisinin anılarını yeniden yorumladığı ve onları tutarlı bir kişilik “resmi” yaratabilmek için yeniden şekillendirdiği bir travma anlatısı olarak incelemektir. Montjoy, sadece geçmişte yaptığı seçimleri anlayabilmek ve bugünkü ben’i hangi seçiminin oluşturduğunu bulmak için otobiyografi kaleme almamış, aynı zamanda hep “tam merkezde” var olan kendi karanlığını/kaybını ve bunun yarattığı baş edilmez korkunun nedenini de anlamak için hayatının belki de son evresinde bu işe kalkışmıştır. Romanda bu karanlık anın resmi tam olarak verilmese de kahramanın kendisi için oluşturduğu bu kişisel anlatısı bir “terapi” olarak işlev görür.
The aim of this study is to analyze Jeanette Winterson’s The Passion and Sexing the Cherry in terms of the feminine symbolic the writer creates in her female characters’ narratives through a process ...of literalizing dead metaphors. Using metaphors in their literal sense, a rhetorical pattern which Regina Barreca calls “metaphor-into-narrative,” is often deemed a subversive tool in women writers’ works to create “laughter”. It shows that women writers often use a metaphor in a conflicting context in their comedic works, and thereby stripping language of its symbolic quality. The present study argues that the marginal subject position of Winterson’s female characters as “misfits” creates a noticeable difference in their discourses and suggests a move from the symbolic order of language to a feminine symbolic. With the examples from The Passion and Sexing the Cherry, the article studies Winterson’s “literalization” to reveal how the writer uses metaphors out of their original contexts not only to create humor but also to destabilize the singular order of language used in historiographic representation by leaving the distinction between what is figurative and what is literal unclear. Winterson’s female characters in The Passion and in Sexing the Cherry are also fitting examples for Bakhtin’s “Fool” with their resistance to join in the discourse of patriarchy and to understand the habitual ways of conceiving the world.
Angiotensin II (Ang II), a key mediator of vascular diseases, is linked to methylglyoxal (MGO) formation, a by‐product of glucose metabolism implicated in vascular complications. The glyoxalase ...system, consisting of glyoxalase 1 (Glo1) and reduced glutathione (GSH), is responsible for detoxifying MGO. This study investigated the effect of Ang II on Glo1 activity and expression in vascular smooth muscle cells (VSMCs). Primary VSMCs were isolated from rat aortas and exposed to Ang II under standard or high glucose conditions. We examined Glo1 activity, expression, intracellular GSH, and methylglyoxal‐derived hydroimidazolone 1 (MG‐H1) levels. We also analyzed the expressions of nuclear factor‐κB (NF‐κB) p65 and nuclear factor erythroid 2‐related factor 2 (Nrf2) as potential regulators of Glo1 expression. The results demonstrated that Ang II reduced Glo1 activity, expression, and GSH levels while increasing MG‐H1 levels in VSMCs. Telmisartan and irbesartan, AT1R blockers, restored Glo1 activity, expression, and GSH levels and alleviated MG‐H1 levels. Treatment with AT1R blockers or inhibitors targeting signaling pathways involved in Ang II‐induced responses mitigated these effects. High glucose exacerbated the reduction in Glo1 activity and expression. In conclusion, this study provides evidence that Ang II reduces Glo1 activity and expression in VSMCs, which may contribute to developing vascular complications in diabetes. AT1R blockers and inhibitors targeting specific signaling pathways show potential in restoring Glo1 function and mitigating MGO‐associated damage. These findings highlight the complex interactions between RAS, MGO, and vascular diseases, highlighting potential therapeutic targets for diabetic vascular complications.
Significance Statement
This study uncovers a crucial link between angiotensin II and vascular complications in diabetes. Angiotensin II was found to suppress an essential protective enzyme, glyoxalase 1, leading to increased levels of harmful methylglyoxal. Importantly, this effect was exacerbated by high glucose levels, resembling hyperglycemic conditions in diabetes. The research sheds light on the mechanisms behind diabetic vascular issues and highlights potential therapeutic strategies, such as angiotensin II receptor blockers and pathway‐specific inhibitors, to restore glyoxalase 1 function. These findings hold promise for future treatments aimed at reducing diabetic vascular complications.
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