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A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma
المؤلفون المشاركون
Ceccarelli, C.
De Luise, Monica
Porcelli, Anna Maria
Guarnieri, Vito
Gasparre, Giuseppe
D'Agruma, Leonardo
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2019، العدد 2019 (31 ديسمبر/كانون الأول 2019)، ص ص. 1-5، 5ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2019-01-09
دولة النشر
مصر
عدد الصفحات
5
التخصصات الرئيسية
الملخص EN
The Von Hippel-Lindau (VHL) syndrome has been rarely associated with renal oncocytomas, and tumors usually show HIF1α chronic stabilization.
By contrast, oncocytomas mainly associated with respiratory chain (RC) defects due to severe mitochondrial DNA (mtDNA) mutations are incapable of stabilizing HIF1α, since oxygen consumption by the RC is dramatically diminished and prolylhydroxylase activity is increased by α-ketoglutarate accumulation following Krebs cycle slowdown.
Here, we investigate the cooccurrence of a pseudohypoxic condition with oncocytic transformation in a case of VHL-associated renal oncocytoma.
While HIF1α was abundant in nuclei concordantly with defects in VHL, negative staining of its targets carbonic anhydrase IX (CAIX) and glucose transporter GLUT1, usually overexpressed in VHL-associated neoplasms, suggested HIF1α to be present in its inactive (hydroxylated) form.
MtDNA sequencing and immunohistochemistry analyses revealed a MT-CO1 stop-gain mutation and cytochrome c oxidase loss.
We suggest that a mitochondrial respiration impairment may lead to hyperhydroxylation of the transcription factor, which we confirmed by specific staining of hydroxylated HIF1α.
Such inactive form hence accumulated in the VHL-deficient tumor, where it may contribute to the benign nature of the neoplasm.
We propose that the protumorigenic role of HIF1α in VHL cancers may be blunted through drugs inhibiting mitochondrial respiratory complexes, such as metformin.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
De Luise, Monica& Guarnieri, Vito& Ceccarelli, C.& D'Agruma, Leonardo& Porcelli, Anna Maria& Gasparre, Giuseppe. 2019. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity،Vol. 2019, no. 2019, pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
De Luise, Monica…[et al.]. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity No. 2019 (2019), pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
De Luise, Monica& Guarnieri, Vito& Ceccarelli, C.& D'Agruma, Leonardo& Porcelli, Anna Maria& Gasparre, Giuseppe. A Nonsense Mitochondrial DNA Mutation Associates with Dysfunction of HIF1α in a Von Hippel-Lindau Renal Oncocytoma. Oxidative Medicine and Cellular Longevity. 2019. Vol. 2019, no. 2019, pp.1-5.
https://search.emarefa.net/detail/BIM-1205450
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1205450
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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