Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats
Carbonic anhydrases constitute a family of metalloenzymes vital for maintaining acid-base balance and regulating pH in physio-pathological processes. These findings suggest carbonic anhydrases as potential therapeutic targets for treating pH-associated disorders, including cerebral ischemia, to miti...
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Elsevier
2025-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844025008370 |
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| author | Sara Amiranda Mariangela Succoio Serenella Anzilotti Ornella Cuomo Tiziana Petrozziello Valentina Tedeschi Arianna Finizio Giorgia Mele Seppo Parkkila Lucio Annunziato Giuseppina De Simone Giuseppe Pignataro Agnese Secondo Nicola Zambrano |
| author_facet | Sara Amiranda Mariangela Succoio Serenella Anzilotti Ornella Cuomo Tiziana Petrozziello Valentina Tedeschi Arianna Finizio Giorgia Mele Seppo Parkkila Lucio Annunziato Giuseppina De Simone Giuseppe Pignataro Agnese Secondo Nicola Zambrano |
| author_sort | Sara Amiranda |
| collection | DOAJ |
| description | Carbonic anhydrases constitute a family of metalloenzymes vital for maintaining acid-base balance and regulating pH in physio-pathological processes. These findings suggest carbonic anhydrases as potential therapeutic targets for treating pH-associated disorders, including cerebral ischemia, to mitigate hypoxia- and reoxygenation-induced neuronal damage. A focus on carbonic anhydrase IX showed that ischemic stress altered subcellular distributions of this enzyme in rodent neuronal populations. Given the enzyme's canonical membrane localization, we implemented pharmacological inhibition using a membrane-impermeant sulfonamide inhibitor in neuronal models of brain ischemia. The treatments exerted neuroprotective effects on neurons from Car9 knockout mice. Moreover, administration of the sulfonamide inhibitor to rats subjected to transient middle cerebral artery occlusion decreased infarct volumes and improved neurological deficits. Our results support the involvement of carbonic anhydrase IX in postischemic damage and pave the way for possible pharmacological interventions with selective inhibitors in the management of brain ischemia. |
| format | Article |
| id | doaj-art-26ba8fd8148b424bb3d3adc131a2c564 |
| institution | Kabale University |
| issn | 2405-8440 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj-art-26ba8fd8148b424bb3d3adc131a2c5642025-02-12T05:31:23ZengElsevierHeliyon2405-84402025-02-01114e42457Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic ratsSara Amiranda0Mariangela Succoio1Serenella Anzilotti2Ornella Cuomo3Tiziana Petrozziello4Valentina Tedeschi5Arianna Finizio6Giorgia Mele7Seppo Parkkila8Lucio Annunziato9Giuseppina De Simone10Giuseppe Pignataro11Agnese Secondo12Nicola Zambrano13Dipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; CEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Napoli, ItalyDipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; CEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Napoli, ItalyDepartment of Human Sciences and Quality of Life Promotion, Università San Raffaele, Rome, ItalyDivision of Pharmacology, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, ItalyDivision of Pharmacology, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, ItalyDivision of Pharmacology, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, ItalyDipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; CEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Napoli, ItalyDipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; CEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Napoli, ItalyFaculty of Medicine and Health Technology, Tampere University, Tampere, Finland; Fimlab Ltd, Tampere University Hospital, Tampere, FinlandSYNLAB SDN, Via Gianturco, Napoli, ItalyIstituto di Biostrutture e Bioimmagini, CNR, Via Pietro Castellino 111, 80131, Napoli, ItalyDivision of Pharmacology, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, ItalyDivision of Pharmacology, Dipartimento di Neuroscienze e Scienze Riproduttive ed Odontostomatologiche, Università degli Studi di Napoli Federico II, Napoli, Italy; Corresponding author.Dipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy; CEINGE Biotecnologie Avanzate Franco Salvatore S.C.aR.L., Napoli, Italy; Corresponding author. Dipartimento di Medicina molecolare e Biotecnologie mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.Carbonic anhydrases constitute a family of metalloenzymes vital for maintaining acid-base balance and regulating pH in physio-pathological processes. These findings suggest carbonic anhydrases as potential therapeutic targets for treating pH-associated disorders, including cerebral ischemia, to mitigate hypoxia- and reoxygenation-induced neuronal damage. A focus on carbonic anhydrase IX showed that ischemic stress altered subcellular distributions of this enzyme in rodent neuronal populations. Given the enzyme's canonical membrane localization, we implemented pharmacological inhibition using a membrane-impermeant sulfonamide inhibitor in neuronal models of brain ischemia. The treatments exerted neuroprotective effects on neurons from Car9 knockout mice. Moreover, administration of the sulfonamide inhibitor to rats subjected to transient middle cerebral artery occlusion decreased infarct volumes and improved neurological deficits. Our results support the involvement of carbonic anhydrase IX in postischemic damage and pave the way for possible pharmacological interventions with selective inhibitors in the management of brain ischemia.http://www.sciencedirect.com/science/article/pii/S2405844025008370HypoxiaBrain ischemiaCarbonic anhydrase IXCarbonic anhydrase inhibitors |
| spellingShingle | Sara Amiranda Mariangela Succoio Serenella Anzilotti Ornella Cuomo Tiziana Petrozziello Valentina Tedeschi Arianna Finizio Giorgia Mele Seppo Parkkila Lucio Annunziato Giuseppina De Simone Giuseppe Pignataro Agnese Secondo Nicola Zambrano Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats Heliyon Hypoxia Brain ischemia Carbonic anhydrase IX Carbonic anhydrase inhibitors |
| title | Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats |
| title_full | Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats |
| title_fullStr | Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats |
| title_full_unstemmed | Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats |
| title_short | Pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of Car9 genetic ablation in a murine setting of oxygen/glucose deprivation followed by re-oxygenation and is associated with improved neuronal function in ischemic rats |
| title_sort | pharmacological inhibition of carbonic anhydrases with a positively charged pyridinium sulfonamide phenocopies the neuroprotective effects of car9 genetic ablation in a murine setting of oxygen glucose deprivation followed by re oxygenation and is associated with improved neuronal function in ischemic rats |
| topic | Hypoxia Brain ischemia Carbonic anhydrase IX Carbonic anhydrase inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2405844025008370 |
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