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)...

Université de Fribourg

PARP inhibition induces Akt-mediated cytoprotective effects through the formation of a mitochondria-targeted phospho-ATM-NEMO-Akt-mTOR signalosome

Tapodi, Antal ; Bognar, Zita ; Szabo, Csaba ; Gallyas, Ferenc ; Sumegi, Balázs ; Hocsak, Enikő

In: Biochemical Pharmacology, 2019, vol. 162, p. 98–108

The cytoprotective effect of poly(ADP-ribose) polymerase 1 (PARP1) inhibition is well documented in various cell types subjected to oxidative stress. Previously, we have demonstrated that PARP1 inhibition activates Akt, and showed that this response plays a critical role in the maintenance of mitochondrial integrity and in cell survival. However, it has not yet been defined how nuclear PARP1...

Université de Fribourg

H2S, a Bacterial Defense Mechanism against the Host Immune Response

Toliver-Kinsky, Tracy ; Cui, Weihua ; Törö, Gabor ; Lee, Seung-Jin ; Shatalin, Konstantin ; Nudler, Evgeny ; Szabo, Csaba

In: Infection and Immunity, 2019, vol. 87, no. 1, p. e00272-18

The biological mediator hydrogen sulfide (H2S) is produced by bacteria and has been shown to be cytoprotective against oxidative stress and to increase the sensitivity of various bacteria to a range of antibiotic drugs. Here we evaluated whether bacterial H2S provides resistance against the immune response, using two bacterial species that are common sources of nosocomial infections,...

Université de Fribourg

Cystathionine γ Lyase Sulfhydrates the RNA Binding Protein Human Antigen R to Preserve Endothelial Cell Function and Delay Atherogenesis

Bibli, Sofia-Iris ; Hu, Jiong ; Sigala, Fragiska ; Wittig, Ilka ; Heidler, Juliana ; Zukunft, Sven ; Tsilimigras, Diamantis I. ; Randriamboavonjy, Voahanginirina ; Wittig, Janina ; Kojonazarov, Baktybek ; Schürmann, Christoph ; Siragusa, Mauro ; Siuda, Daniel ; Luck, Bert ; Malik, Randa Abdel ; Filis, Konstantinos A. ; Zografos, George ; Chen, Chen ; Wang, Dao Wen ; Pfeilschifter, Josef ; Brandes, Ralf P. ; Szabo, Csaba ; Papapetropoulos, Andreas ; Fleming, Ingrid

In: Circulation, 2019, vol. 139, no. 1, p. 101–114

Hydrogen sulfide (H2S), generated by cystathionine γ lyase (CSE), is an important endogenous regulator of vascular function. The aim of the present study was to investigate the control and consequences of CSE activity in endothelial cells under physiological and proatherogenic conditions.

Université de Fribourg

Interaction of the hydrogen sulfide system with the oxytocin system in the injured mouse heart

Merz, Tamara ; Lukaschewski, Britta ; Wigger, Daniela ; Rupprecht, Aileen ; Wepler, Martin ; Gröger, Michael ; Hartmann, Clair ; Whiteman, Matthew ; Szabo, Csaba ; Wang, Rui ; Waller, Christiane ; Radermacher, Peter ; McCook, Oscar

In: Intensive Care Medicine Experimental, 2018, vol. 6, no. 1, p. 41

Both the hydrogen sulfide/cystathionine-γ-lyase (H2S/CSE) and oxytocin/oxytocin receptor (OT/OTR) systems have been reported to be cardioprotective. H2S can stimulate OT release, thereby affecting blood volume and pressure regulation. Systemic hyper-inflammation after blunt chest trauma is enhanced in cigarette smoke (CS)-exposed CSE−/− mice compared to wildtype (WT). CS increases...

Université de Fribourg

Cystathionine-γ-lyase expression is associated with mitochondrial respiration during sepsis-induced acute kidney injury in swine with atherosclerosis

Merz, Tamara ; Wepler, Martin ; Nußbaum, Benedikt ; Vogt, Josef ; Calzia, Enrico ; Wang, Rui ; Szabo, Csaba ; Radermacher, Peter ; McCook, Oscar

In: Intensive Care Medicine Experimental, 2018, vol. 6, no. 1, p. 43

Sepsis is associated with disturbed glucose metabolism and reduced mitochondrial activity and biogenesis, ultimately leading to multiple organ dysfunction, e.g., acute kidney injury (AKI). Cystathionine-γ-lyase (CSE), the major cardiovascular source of endogenous H2S release, is implicated in the regulation of glucose metabolism and mitochondrial activity through a PGC1α-dependent...