title: Transcriptional alterations of ET-1 axis and DNA damage in lung tissue of a rat obesity model.
abstract: Obesity has been implicated in the development of many cancers. This can lead to genome damage, especially in the form of double-strand break, the presence of which is now easily detected through nuclear phosphorylation of histone H2AX (γ-H2AX) focus assay. Recently, the endothelin (ET) axis has also been shown to have a role in the growth and progression of several tumors, including lung cancer. The aim of this study was to evaluate the ET-1 system transcriptional alterations and γ-H2AX in lung tissue of Zucker rats subdivided into obese (O, n=22) and controls (CO, n=18) rats: under either fasting conditions (CO(fc)-O(fc)) or acute hyperglycemia (CO(AH)-O(AH)). Significantly higher prepro-ET-1 (p=0.05) and ET-converting enzyme (ECE)-2 mRNA expression was observed in O with respect to CO. A significant positive association was observed between prepro-ET-1 and ET-A in the whole rat population (p=0.009) or in the obese group alone (p=0.007). The levels of γ-H2AX in O and in O(AH) rats were significantly higher (p=0.019) than in the corresponding CO and CO(AH) rats (p=0.038). The study shows an inappropriate secretion of ET-1 in O animals with a parallel DNA damage in their lungs, providing novel mechanisms by which ET receptor antagonist may exert organ protection.
authors.affiliation: 1 Cardiovascular Biochemistry Laboratories, CNR Institute of Clinical Physiology , Pisa, Italy .
authors.forename: Silvia
authors.initials: S
authors.lastname: Del Ry
authors.forename: Manuela
authors.initials: M
authors.lastname: Cabiati
authors.forename: Costanza
authors.initials: C
authors.lastname: Salvadori
authors.forename: Letizia
authors.initials: L
authors.lastname: Guiducci
authors.forename: Chiara
authors.initials: C
authors.lastname: Caselli
authors.forename: Tommaso
authors.initials: T
authors.lastname: Prescimone
authors.forename: Maria Sole
authors.initials: MS
authors.lastname: Facioni
authors.forename: Alessia
authors.initials: A
authors.lastname: Azzarà
authors.forename: Anna
authors.initials: A
authors.lastname: Chiaramonte
authors.forename: Stefano
authors.initials: S
authors.lastname: Mazzoni
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Bruschi
authors.forename: Daniela
authors.initials: D
authors.lastname: Giannessi
authors.forename: Roberto
authors.initials: R
authors.lastname: Scarpato
mesh_terms: D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D004249:DNA Damage; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000235:genetics* / Q000378:metabolism; D000072396:Endothelin-Converting Enzymes; D006657:Histones / Q000378:metabolism; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D008168:Lung / Q000378:metabolism*; D008297:Male; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000235:genetics* / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011924:Rats, Zucker; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D001786:Blood Glucose; D019332:Endothelin-1; D006657:Histones; D007328:Insulin; D010750:Phosphoproteins; D012333:RNA, Messenger; C577575:gamma-H2AX protein, rat; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes