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Role of connexins and pannexins in cardiovascular physiology

Meens, Merlijn ; Kwak, Brenda ; Duffy, Heather

In: Cellular and Molecular Life Sciences, 2015, vol. 72, no. 15, p. 2779-2792

Université de Fribourg

Mechanism of cystathionine-β-synthase inhibition by disulfiram : The role of bis(N,N-diethyldithiocarbamate)-copper(II)

Zuhra, Karim ; Panagaki, Theodora ; B.Randi, Elisa ; Augsburger, Fiona ; Blondel, Marc ; Friocourt, Gaelle ; Herault, Yann ; Szabo, Csaba

In: Biochemical Pharmacology, 2020, vol. 182, p. 114267

Background: Hydrogen sulfide (H2S) is an endogenous mammalian gasotransmitter. Cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE) and 3- mercaptopyruvate sulfurtransferase (3-MST) are the principal enzymes responsible for its biogenesis. A recent yeast screen suggested that disulfiram (a well-known inhibitor of aldehyde dehydrogenase and a clinically used drug in the treatment of...

Université de Fribourg

Effects of the poly(ADP-ribose) polymerase inhibitor olaparib in cerulein-induced pancreatitis

Ahmad, Akbar ; Haas De Mello, Aline ; Szczesny, Bartosz ; Törö, Gábor ; Marcatti, Michela ; Druzhyna, Nadiya ; Liaudet, Lucas ; Tarantini, Stefano ; Salomao, Reinaldo ; Garcia Soriano, Francisco ; Szabo, Csaba

In: Shock, 2020, vol. 53, no. 5, p. 653–665

Objective: Activation of the constitutive nuclear and mitochondrial enzyme poly (ADP- ribose) polymerase (PARP) has been implicated in the pathogenesis of cell dysfunction, inflammation, and organ failure in various forms of critical illness. The objective of our study was to evaluate the efficacy and safety of the clinically approved PARP inhibitor olaparib in an experimental model of...

Université de Fribourg

Poly(ADP-ribose) polymerase inhibition in acute lung injury. A reemerging concept

Szabo, Csaba ; Martins, Vanessa ; Liaudet, Lucas

In: American Journal of Respiratory Cell and Molecular Biology, 2020, vol. 63, no. 5, p. 571–590

PARP1, the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription, and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI) and that pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits emerged over 20 years ago....

Université de Fribourg

Cystathionine-β-synthase: molecular regulation and pharmacological inhibition

Zuhra, Karim ; Augsburger, Fiona ; Majtan, Tomas ; Szabo, Csaba

In: Biomolecules, 2020, vol. 10, no. 5, p. 697

Cystathionine-β-synthase (CBS), the first (and rate-limiting) enzyme in the transsulfuration pathway, is an important mammalian enzyme in health and disease. Its biochemical functions under physiological conditions include the metabolism of homocysteine (a cytotoxic molecule and cardiovascular risk factor) and the generation of hydrogen sulfide (H2S), a gaseous biological mediator with...

Université de Fribourg

Role of akt activation in PARP inhibitor resistance in cancer

Gallyas, Ferenc ; Sumegi, Balazs ; Szabo, Csaba

In: Cancers, 2020, vol. 12, no. 3, p. 532

Poly(ADP-ribose) polymerase (PARP) inhibitors have recently been introduced in the therapy of several types of cancers not responding to conventional treatments. However, de novo and acquired PARP inhibitor resistance is a significant limiting factor in the clinical therapy, and the underlying mechanisms are not fully understood. Activity of the cytoprotective phosphatidylinositol-3 kinase...

Université de Fribourg

Overproduction of H2S, generated by CBS, inhibits mitochondrial Complex IV and suppresses oxidative phosphorylation in Down syndrome

Panagaki, Theodora ; Randi, Elisa B. ; Augsburger, Fiona ; Szabo, Csaba

In: Proceedings of the National Academy of Sciences, 2019, p. 201911895

Down syndrome (DS) is associated with significant perturbances in mitochondrial function. Here we tested the hypothesis that the suppression of mitochondrial electron transport in DS cells is due to high expression of cystathionine-β-synthase (CBS) and subsequent overproduction of the gaseous transmitter hydrogen sulfide (H2S). Fibroblasts from DS individuals showed higher CBS expression...

Université de Fribourg

The PARP inhibitor olaparib exerts beneficial effects in mice subjected to cecal ligature and puncture and in cells subjected to oxidative stress without impairing DNA integrity: A potential opportunity for repurposing a clinically used oncological drug for the experimental therapy of sepsis

Ahmad, Akbar ; Vieira, Juliana de Camargo ; Mello, Aline Haas de ; Lima, Thais Martins de ; Ariga, Suely Kubo ; Barbeiro, Denise Frediani ; Barbeiro, Hermes Vieira ; Szczesny, Bartosz ; Törö, Gábor ; Druzhyna, Nadiya ; B.Randi, Elisa ; Marcatti, Michela ; Toliver-Kinsky, Tracy ; Kiss, András ; Liaudet, Lucas ; Salomao, Reinaldo ; Soriano, Francisco Garcia ; Szabo, Csaba

In: Pharmacological Research, 2019, vol. 145, p. 104263

Poly(ADP-ribose) polymerase (PARP) is involved in the pathogenesis of cell dysfunction, inflammation and organ failure during septic shock. The goal of the current study was to investigate the efficacy and safety of the clinically approved PARP inhibitor olaparib in experimental models of oxidative stress in vitro and in sepsis in vivo. In mice subjected to cecal ligation and puncture (CLP)...