New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation

To date, a major research effort on Behçet’s syndrome (BS) has been concentrated on immunological aspects. Little is known about the metabolic reprogramming in BS. Citrate is an intermediary metabolite synthesized in mitochondria, and when transported into the cytosol by the mitochondrial citrate ca...

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Main Authors: Anna Santarsiero, Pietro Leccese, Paolo Convertini, Angela Padula, Paolo Abriola, Salvatore D’Angelo, Faustino Bisaccia, Vittoria Infantino
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2018/1419352
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author Anna Santarsiero
Pietro Leccese
Paolo Convertini
Angela Padula
Paolo Abriola
Salvatore D’Angelo
Faustino Bisaccia
Vittoria Infantino
author_facet Anna Santarsiero
Pietro Leccese
Paolo Convertini
Angela Padula
Paolo Abriola
Salvatore D’Angelo
Faustino Bisaccia
Vittoria Infantino
author_sort Anna Santarsiero
collection DOAJ
description To date, a major research effort on Behçet’s syndrome (BS) has been concentrated on immunological aspects. Little is known about the metabolic reprogramming in BS. Citrate is an intermediary metabolite synthesized in mitochondria, and when transported into the cytosol by the mitochondrial citrate carrier—SLC25A1-encoded protein—it is cleaved into acetyl-CoA and oxaloacetate by ATP citrate lyase (ACLY). In induced macrophages, mitochondrial citrate is necessary for the production of inflammatory mediators. The aim of our study was to evaluate SLC25A1 and ACLY expression levels in BS patients. Following a power analysis undertaken on few random samples, the number of enrolled patients was set. Thirty-nine consecutive BS patients fulfilling ISG criteria, and 21 healthy controls suitable for age and sex were recruited. BS patients were divided into two groups according to the presence (active) or absence (inactive) of clinical manifestations. Real-time PCR experiments were performed on PBMCs to quantify SLC25A1 and ACLY mRNA levels. Data processing through the Kruskal-Wallis test and Dunn’s multiple comparison test as post hoc showed higher SLC25A1 and ACLY mRNA levels in BS patients compared to those in healthy controls. Therefore, SLC25A1 and ACLY upregulation suggests that metabolic reprogramming in BS involves the citrate pathway dysregulation.
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spelling doaj-art-f5c328f1af344cb58d56e226443949c42025-02-03T01:22:04ZengWileyMediators of Inflammation0962-93511466-18612018-01-01201810.1155/2018/14193521419352New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway DysregulationAnna Santarsiero0Pietro Leccese1Paolo Convertini2Angela Padula3Paolo Abriola4Salvatore D’Angelo5Faustino Bisaccia6Vittoria Infantino7Department of Science, University of Basilicata, Potenza, ItalyRheumatology Department of Lucania, Rheumatology Institute of Lucania (IReL), San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, ItalyDepartment of Science, University of Basilicata, Potenza, ItalyRheumatology Department of Lucania, Rheumatology Institute of Lucania (IReL), San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, ItalyDepartment of Science, University of Basilicata, Potenza, ItalyRheumatology Department of Lucania, Rheumatology Institute of Lucania (IReL), San Carlo Hospital of Potenza and Madonna delle Grazie Hospital of Matera, Potenza, ItalyDepartment of Science, University of Basilicata, Potenza, ItalyDepartment of Science, University of Basilicata, Potenza, ItalyTo date, a major research effort on Behçet’s syndrome (BS) has been concentrated on immunological aspects. Little is known about the metabolic reprogramming in BS. Citrate is an intermediary metabolite synthesized in mitochondria, and when transported into the cytosol by the mitochondrial citrate carrier—SLC25A1-encoded protein—it is cleaved into acetyl-CoA and oxaloacetate by ATP citrate lyase (ACLY). In induced macrophages, mitochondrial citrate is necessary for the production of inflammatory mediators. The aim of our study was to evaluate SLC25A1 and ACLY expression levels in BS patients. Following a power analysis undertaken on few random samples, the number of enrolled patients was set. Thirty-nine consecutive BS patients fulfilling ISG criteria, and 21 healthy controls suitable for age and sex were recruited. BS patients were divided into two groups according to the presence (active) or absence (inactive) of clinical manifestations. Real-time PCR experiments were performed on PBMCs to quantify SLC25A1 and ACLY mRNA levels. Data processing through the Kruskal-Wallis test and Dunn’s multiple comparison test as post hoc showed higher SLC25A1 and ACLY mRNA levels in BS patients compared to those in healthy controls. Therefore, SLC25A1 and ACLY upregulation suggests that metabolic reprogramming in BS involves the citrate pathway dysregulation.http://dx.doi.org/10.1155/2018/1419352
spellingShingle Anna Santarsiero
Pietro Leccese
Paolo Convertini
Angela Padula
Paolo Abriola
Salvatore D’Angelo
Faustino Bisaccia
Vittoria Infantino
New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
Mediators of Inflammation
title New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
title_full New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
title_fullStr New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
title_full_unstemmed New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
title_short New Insights into Behçet’s Syndrome Metabolic Reprogramming: Citrate Pathway Dysregulation
title_sort new insights into behcet s syndrome metabolic reprogramming citrate pathway dysregulation
url http://dx.doi.org/10.1155/2018/1419352
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