Alessandra Pagliarani - Academia.edu (original) (raw)
Uploads
Papers by Alessandra Pagliarani
Pharmacological Research, Apr 1, 2021
Sulfide affects the mitochondrial respiration, the Ca2+-activated F1FO-ATPase activity and the pe... more Sulfide affects the mitochondrial respiration, the Ca2+-activated F1FO-ATPase activity and the permeability transition pore but does not change the Mg2+-activated F1FO-ATPase activity in swine heart mitochondria.
Annals of the New York Academy of Sciences, 2019
The properties of the mitochondrial F 1 F O-ATPase catalytic site, which can bind Mg 2+ , Mn 2+ o... more The properties of the mitochondrial F 1 F O-ATPase catalytic site, which can bind Mg 2+ , Mn 2+ or Ca 2+ and hydrolyses ATP, are explored by inhibition kinetic analyses to cast light on the Ca 2+-activated F 1 F O-ATPase connection with the permeability transition pore (PTP), which initiates cascade events leading to cell death. While the natural cofactor Mg 2+ activates the F 1 F O-ATPase in competition with Mn 2+ , Ca 2+ is uncompetitive inhibitor in the presence of Mg 2+. Selective F 1 inhibitors, namely NBD-Cl, piceatannol, resveratrol and quercetin (Is-F 1), exert different mechanisms (mixed/uncompetitive inhibition) on the Ca 2+-or Mg 2+-activated F 1 F O-ATPase, thus suggesting that the catalytic mechanism changes when Mg 2+ is replaced by Ca 2+. In purified F 1 domain, the Ca 2+-activated F 1-ATPase maintains the Is-F 1 sensitivity. The enzyme inhibition is accompanied by the maintenance of the mitochondrial calcium retention capacity and membrane potential. The data strengthen the Ca 2+-activated F 1 F O-ATPase structural relationship with the PTP, in turn involved in physiopathological cellular changes.
Although the bactericidal properties of the germicide employed on clams are tightly linked to its... more Although the bactericidal properties of the germicide employed on clams are tightly linked to its oxidative power, confirmed by the oxidative stress detected in in vitro treated haemocytes, the similarity of VOC profiles and TBARs levels in treated and control clams suggest that the organoleptic features are unaffected, thus shouldering this treatment before clam introduction into the market
67th National Congress of the Italian Physiological Society, 2016
Although the bactericidal properties of the germicide employed on clams are tightly linked to its... more Although the bactericidal properties of the germicide employed on clams are tightly linked to its oxidative power, confirmed by the oxidative stress detected in in vitro treated haemocytes, the similarity of VOC profiles and TBARs levels in treated and control clams suggest that the organoleptic features are unaffected, thus shouldering this treatment before clam introduction into the market
45° Congresso della Società Italiana di Biologia Marina, 2014
47° Congresso della Società Italiana di Biologia Marina, 2016
L'esposizione di vongole ad un germicida commerciale (1000 ppm) per 3 ore per ridurre la cari... more L'esposizione di vongole ad un germicida commerciale (1000 ppm) per 3 ore per ridurre la carica batterica non modifica l'attivit\ue0 catalasica nella ghiandola digestiva. Invece dosi molto inferiori del germicida saggiate in vitro su colture di emociti alterano profondamente la morfologia e la funzionalit\ue0 cellulare. Pertanto questo trattamento sembra applicabile in vivo, anche se in vitro \ue8 chiaramente immunotossico.The exposure of clams to 1000 ppm strong oxidizing commercial germicide for 3 hours to reduce bacterial load did not modify the catalase activitiy in the midgut gland. Conversely, far lower germicide doses strongly affected the morphology and functionality of in vitro tested cultured haemocytes. The germicide treatment may be promising in vivo, in spite of its in vitro immunotoxicity
Small inorganic compounds able to prevent the mitochondrial permeability transition, the master p... more Small inorganic compounds able to prevent the mitochondrial permeability transition, the master player in apoptosis and necrosis, are increasingly considered as beneficial tools in cytoprotection. Nitrite, a known cellular nitric oxide reservoir, has a recognized role in cardioprotection, but the molecular mechanisms of its action are not thoroughly understood. Mitochondrial permeability changes are known to constitute the molecular bases of human cardiac diseases and pathologies related to mitochondrial dysfunctions. In turn oxidative stress and mitochondrial damage are related issues in degenerative and cardiovascular diseases. Assumed that the mitochondrial F1FO complex is structurally or functionally involved in the mitochondrial permeability transition pore (MPTP), which triggers the mitochondrial permeability transition, nitrite effects on the enzyme complex may be exploited to shut the MPTP. Many clues suggest that nitrite may prevent or limit cell death by modulating the F1FO complex. Accordingly, nitrite decreases the ATPase activity stimulated by Ca2+, it is ineffective on the Mg-ATPase up to 2 mM and the enzyme inhibition is apparently enhanced under oxidative stress conditions. Through the inhibition of the calcium-activated F1FO complex, nitrite would shut the MPTP, which is likely to be related to the calcium-dependent functioning mode of the F1FO complex, and limit mitochondrial impairment and cell death under physio-pathological conditions
Riunione annuale gruppo SIB Biochimica Marina e dell'ambiente SIBMA 2010, 2010
Small inorganic compounds able to prevent the mitochondrial permeability transition, the master p... more Small inorganic compounds able to prevent the mitochondrial permeability transition, the master player in apoptosis and necrosis, are increasingly considered as beneficial tools in cytoprotection. Nitrite, a known cellular nitric oxide reservoir, has a recognized role in cardioprotection, but the molecular mechanisms of its action are not thoroughly understood. Mitochondrial permeability changes are known to constitute the molecular bases of human cardiac diseases and pathologies related to mitochondrial dysfunctions. In turn oxidative stress and mitochondrial damage are related issues in degenerative and cardiovascular diseases. Assumed that the mitochondrial F1FO complex is structurally or functionally involved in the mitochondrial permeability transition pore (MPTP), which triggers the mitochondrial permeability transition, nitrite effects on the enzyme complex may be exploited to shut the MPTP. Many clues suggest that nitrite may prevent or limit cell death by modulating the F1FO complex. Accordingly, nitrite decreases the ATPase activity stimulated by Ca2+, it is ineffective on the Mg-ATPase up to 2 mM and the enzyme inhibition is apparently enhanced under oxidative stress conditions. Through the inhibition of the calcium-activated F1FO complex, nitrite would shut the MPTP, which is likely to be related to the calcium-dependent functioning mode of the F1FO complex, and limit mitochondrial impairment and cell death under physio-pathological conditions
Nella ghiandola digestiva di mitilo \ue8 stato valutato l'effetto dello stagno tributile (TBT... more Nella ghiandola digestiva di mitilo \ue8 stato valutato l'effetto dello stagno tributile (TBT) sulla Mg-ATPasi mitocondriale, enzima chiave del metabolismo energetico cellulare e bersaglio del TBT in mammiferi, lieviti e batteri. Anche nella ghiandola digestiva di mitilo la Mg-ATPasi si conferma bersaglio sensibile all'azione tossica del TBT. L'inibizione del complesso FOF1 potrebbe essere correlata ad altre manifestazioni tossiche del TBT e giustificare almeno in parte la riduzione di produttivit\ue0 delle popolazioni esposte al contaminante e nelle quali la produzione cellulare di ATP pu\uf2 risultare seriamente compromessa
Biochemical and Biological Effects of Organotins, 2012
Pharmacological Research, 2021
In mammalian cells enzymatic and non-enzymatic pathways produce H2S, a gaseous transmitter which ... more In mammalian cells enzymatic and non-enzymatic pathways produce H2S, a gaseous transmitter which recently emerged as promising therapeutic agent and modulator of mitochondrial bioenergetics. To explore this topic, the H2S donor NaHS, at micromolar concentrations, was tested on swine heart mitochondria. NaHS did not affect the F1FO-ATPase activated by the natural cofactor Mg 2 , but, when Mg 2+ was replaced by Ca 2+ , a slight 15% enzyme inhibition at 100 µM NaHS was shown. Conversely, both the NADH-O2 and succinate-O2 oxidoreductase activities were totally inhibited by 200 μM NaHS with IC50 values of 61.6±4.1 and 16.5±4.6 μM NaHS, respectively. Since the mitochondrial respiration was equally inhibited by NaHS at both first or second respiratory substrates sites, the H2S generation may prevent the electron transfer from complexes I and II to downhill respiratory chain complexes, probably because H2S competes with O2 in complex IV, thus reducing membrane potential as a consequence of the cytochrome c oxidase activity inhibition. The Complex IV blockage by H2S was consistent with the linear concentration-dependent NADH-O2 oxidoreductase inhibition and exponential succinate-O2 oxidoreductase inhibition by NaHS, whereas the coupling between substrate oxidation and phosphorylation was unaffected by NaHS. Even if H2S is known to cause sulfhydration of cysteine residues, thiol oxidizing (GSSG) or reducing (DTE) agents, did not affect the F1FO-ATPase activities and mitochondrial respiration, thus ruling out any involvement of post-translational modifications of thiols. The permeability transition pore, the lethal channel which forms when the F1FO-ATPase is stimulated by Ca 2+ , did not open in the presence of NaHS, which shows a similar effect to ruthenium red, thus suggesting a putative Ca 2+ transport cycle inhibition.
Biochimie, 2021
Mitochondrial F1FO-ATPase and permeability transition pore response to sulfide in the midgut glan... more Mitochondrial F1FO-ATPase and permeability transition pore response to sulfide in the midgut gland of Mytilus galloprovincialis
Pharmacological Research, Apr 1, 2021
Sulfide affects the mitochondrial respiration, the Ca2+-activated F1FO-ATPase activity and the pe... more Sulfide affects the mitochondrial respiration, the Ca2+-activated F1FO-ATPase activity and the permeability transition pore but does not change the Mg2+-activated F1FO-ATPase activity in swine heart mitochondria.
Annals of the New York Academy of Sciences, 2019
The properties of the mitochondrial F 1 F O-ATPase catalytic site, which can bind Mg 2+ , Mn 2+ o... more The properties of the mitochondrial F 1 F O-ATPase catalytic site, which can bind Mg 2+ , Mn 2+ or Ca 2+ and hydrolyses ATP, are explored by inhibition kinetic analyses to cast light on the Ca 2+-activated F 1 F O-ATPase connection with the permeability transition pore (PTP), which initiates cascade events leading to cell death. While the natural cofactor Mg 2+ activates the F 1 F O-ATPase in competition with Mn 2+ , Ca 2+ is uncompetitive inhibitor in the presence of Mg 2+. Selective F 1 inhibitors, namely NBD-Cl, piceatannol, resveratrol and quercetin (Is-F 1), exert different mechanisms (mixed/uncompetitive inhibition) on the Ca 2+-or Mg 2+-activated F 1 F O-ATPase, thus suggesting that the catalytic mechanism changes when Mg 2+ is replaced by Ca 2+. In purified F 1 domain, the Ca 2+-activated F 1-ATPase maintains the Is-F 1 sensitivity. The enzyme inhibition is accompanied by the maintenance of the mitochondrial calcium retention capacity and membrane potential. The data strengthen the Ca 2+-activated F 1 F O-ATPase structural relationship with the PTP, in turn involved in physiopathological cellular changes.
Although the bactericidal properties of the germicide employed on clams are tightly linked to its... more Although the bactericidal properties of the germicide employed on clams are tightly linked to its oxidative power, confirmed by the oxidative stress detected in in vitro treated haemocytes, the similarity of VOC profiles and TBARs levels in treated and control clams suggest that the organoleptic features are unaffected, thus shouldering this treatment before clam introduction into the market
67th National Congress of the Italian Physiological Society, 2016
Although the bactericidal properties of the germicide employed on clams are tightly linked to its... more Although the bactericidal properties of the germicide employed on clams are tightly linked to its oxidative power, confirmed by the oxidative stress detected in in vitro treated haemocytes, the similarity of VOC profiles and TBARs levels in treated and control clams suggest that the organoleptic features are unaffected, thus shouldering this treatment before clam introduction into the market
45° Congresso della Società Italiana di Biologia Marina, 2014
47° Congresso della Società Italiana di Biologia Marina, 2016
L'esposizione di vongole ad un germicida commerciale (1000 ppm) per 3 ore per ridurre la cari... more L'esposizione di vongole ad un germicida commerciale (1000 ppm) per 3 ore per ridurre la carica batterica non modifica l'attivit\ue0 catalasica nella ghiandola digestiva. Invece dosi molto inferiori del germicida saggiate in vitro su colture di emociti alterano profondamente la morfologia e la funzionalit\ue0 cellulare. Pertanto questo trattamento sembra applicabile in vivo, anche se in vitro \ue8 chiaramente immunotossico.The exposure of clams to 1000 ppm strong oxidizing commercial germicide for 3 hours to reduce bacterial load did not modify the catalase activitiy in the midgut gland. Conversely, far lower germicide doses strongly affected the morphology and functionality of in vitro tested cultured haemocytes. The germicide treatment may be promising in vivo, in spite of its in vitro immunotoxicity
Small inorganic compounds able to prevent the mitochondrial permeability transition, the master p... more Small inorganic compounds able to prevent the mitochondrial permeability transition, the master player in apoptosis and necrosis, are increasingly considered as beneficial tools in cytoprotection. Nitrite, a known cellular nitric oxide reservoir, has a recognized role in cardioprotection, but the molecular mechanisms of its action are not thoroughly understood. Mitochondrial permeability changes are known to constitute the molecular bases of human cardiac diseases and pathologies related to mitochondrial dysfunctions. In turn oxidative stress and mitochondrial damage are related issues in degenerative and cardiovascular diseases. Assumed that the mitochondrial F1FO complex is structurally or functionally involved in the mitochondrial permeability transition pore (MPTP), which triggers the mitochondrial permeability transition, nitrite effects on the enzyme complex may be exploited to shut the MPTP. Many clues suggest that nitrite may prevent or limit cell death by modulating the F1FO complex. Accordingly, nitrite decreases the ATPase activity stimulated by Ca2+, it is ineffective on the Mg-ATPase up to 2 mM and the enzyme inhibition is apparently enhanced under oxidative stress conditions. Through the inhibition of the calcium-activated F1FO complex, nitrite would shut the MPTP, which is likely to be related to the calcium-dependent functioning mode of the F1FO complex, and limit mitochondrial impairment and cell death under physio-pathological conditions
Riunione annuale gruppo SIB Biochimica Marina e dell'ambiente SIBMA 2010, 2010
Small inorganic compounds able to prevent the mitochondrial permeability transition, the master p... more Small inorganic compounds able to prevent the mitochondrial permeability transition, the master player in apoptosis and necrosis, are increasingly considered as beneficial tools in cytoprotection. Nitrite, a known cellular nitric oxide reservoir, has a recognized role in cardioprotection, but the molecular mechanisms of its action are not thoroughly understood. Mitochondrial permeability changes are known to constitute the molecular bases of human cardiac diseases and pathologies related to mitochondrial dysfunctions. In turn oxidative stress and mitochondrial damage are related issues in degenerative and cardiovascular diseases. Assumed that the mitochondrial F1FO complex is structurally or functionally involved in the mitochondrial permeability transition pore (MPTP), which triggers the mitochondrial permeability transition, nitrite effects on the enzyme complex may be exploited to shut the MPTP. Many clues suggest that nitrite may prevent or limit cell death by modulating the F1FO complex. Accordingly, nitrite decreases the ATPase activity stimulated by Ca2+, it is ineffective on the Mg-ATPase up to 2 mM and the enzyme inhibition is apparently enhanced under oxidative stress conditions. Through the inhibition of the calcium-activated F1FO complex, nitrite would shut the MPTP, which is likely to be related to the calcium-dependent functioning mode of the F1FO complex, and limit mitochondrial impairment and cell death under physio-pathological conditions
Nella ghiandola digestiva di mitilo \ue8 stato valutato l'effetto dello stagno tributile (TBT... more Nella ghiandola digestiva di mitilo \ue8 stato valutato l'effetto dello stagno tributile (TBT) sulla Mg-ATPasi mitocondriale, enzima chiave del metabolismo energetico cellulare e bersaglio del TBT in mammiferi, lieviti e batteri. Anche nella ghiandola digestiva di mitilo la Mg-ATPasi si conferma bersaglio sensibile all'azione tossica del TBT. L'inibizione del complesso FOF1 potrebbe essere correlata ad altre manifestazioni tossiche del TBT e giustificare almeno in parte la riduzione di produttivit\ue0 delle popolazioni esposte al contaminante e nelle quali la produzione cellulare di ATP pu\uf2 risultare seriamente compromessa
Biochemical and Biological Effects of Organotins, 2012
Pharmacological Research, 2021
In mammalian cells enzymatic and non-enzymatic pathways produce H2S, a gaseous transmitter which ... more In mammalian cells enzymatic and non-enzymatic pathways produce H2S, a gaseous transmitter which recently emerged as promising therapeutic agent and modulator of mitochondrial bioenergetics. To explore this topic, the H2S donor NaHS, at micromolar concentrations, was tested on swine heart mitochondria. NaHS did not affect the F1FO-ATPase activated by the natural cofactor Mg 2 , but, when Mg 2+ was replaced by Ca 2+ , a slight 15% enzyme inhibition at 100 µM NaHS was shown. Conversely, both the NADH-O2 and succinate-O2 oxidoreductase activities were totally inhibited by 200 μM NaHS with IC50 values of 61.6±4.1 and 16.5±4.6 μM NaHS, respectively. Since the mitochondrial respiration was equally inhibited by NaHS at both first or second respiratory substrates sites, the H2S generation may prevent the electron transfer from complexes I and II to downhill respiratory chain complexes, probably because H2S competes with O2 in complex IV, thus reducing membrane potential as a consequence of the cytochrome c oxidase activity inhibition. The Complex IV blockage by H2S was consistent with the linear concentration-dependent NADH-O2 oxidoreductase inhibition and exponential succinate-O2 oxidoreductase inhibition by NaHS, whereas the coupling between substrate oxidation and phosphorylation was unaffected by NaHS. Even if H2S is known to cause sulfhydration of cysteine residues, thiol oxidizing (GSSG) or reducing (DTE) agents, did not affect the F1FO-ATPase activities and mitochondrial respiration, thus ruling out any involvement of post-translational modifications of thiols. The permeability transition pore, the lethal channel which forms when the F1FO-ATPase is stimulated by Ca 2+ , did not open in the presence of NaHS, which shows a similar effect to ruthenium red, thus suggesting a putative Ca 2+ transport cycle inhibition.
Biochimie, 2021
Mitochondrial F1FO-ATPase and permeability transition pore response to sulfide in the midgut glan... more Mitochondrial F1FO-ATPase and permeability transition pore response to sulfide in the midgut gland of Mytilus galloprovincialis