{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:19:29Z","timestamp":1762161569110,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T00:00:00Z","timestamp":1596067200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In an in vitro Ca2+-induced cataract model, the progression of opacification is paralleled by a rapid decrease of the endogenous levels of spermidine (SPD) and an increase of transglutaminase type 2 (TG2, EC 2.3.2.13)-catalyzed lens crystallins cross-linking by protein-bound N1-N8-bis(\u03b3-glutamyl) SPD. This pattern was reversed adding exogenous SPD to the incubation resulting in a delayed loss of transparency of the rabbit lens. The present report shows evidence on the main incorporation of SPD by the catalytic activity of TG2, toward \u03b2H-crystallins and in particular to the \u03b2B2- and mostly in \u03b2B3-crystallins. The increase of endogenous SPD in the cultured rabbit lens showed the activation of a flavin adenine dinucleotide (FAD)-dependent polyamine oxidases (PAO EC 1.5.3.11). As it is known that FAD-PAO degrades the N8-terminal reactive portion of N1-mono(\u03b3-glutamyl) SPD, the protein-bound N8-mono(\u03b3-glutamyl) SPD was found the mainly available derivative for the potential formation of \u03b2B3-crystallins cross-links by protein-bound N1-N8-bis(\u03b3-glutamyl)SPD. In conclusion, FAD-PAO degradation of the N8-terminal reactive residue of the crystallins bound N1-mono(\u03b3-glutamyl)SPD together with the increased concentration of exogenous SPD, leading to saturation of glutamine residues on the substrate proteins, drastically reduces N1-N8-bis(\u03b3-glutamyl)SPD crosslinks formation, preventing crystallins polymerization and avoiding rabbit lens opacification. The ability of SPD and MDL 72527 to modulate the activities of TG2 and FAD-PAO involved in the mechanism of lens opacification suggests a potential strategy for the prevention of senile cataract.<\/jats:p>","DOI":"10.3390\/ijms21155427","type":"journal-article","created":{"date-parts":[[2020,7,30]],"date-time":"2020-07-30T12:15:38Z","timestamp":1596111338000},"page":"5427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed \u03b2H-Crystallins Polymerization in Calcium-Induced Experimental Cataract"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0029-2205","authenticated-orcid":false,"given":"Carlo","family":"Mischiati","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences and Surgical Specialties, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giordana","family":"Feriotto","sequence":"additional","affiliation":[{"name":"Department of Chemical and Pharmaceutical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5001-285X","authenticated-orcid":false,"given":"Claudio","family":"Tabolacci","sequence":"additional","affiliation":[{"name":"Department of Oncology and Molecular Medicine, Istituto Superiore di Sanit\u00e0, 00161 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6776-2737","authenticated-orcid":false,"given":"Fabio","family":"Domenici","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences and Technology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonia","family":"Melino","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences and Technology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Borromeo","sequence":"additional","affiliation":[{"name":"Department of Physics, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2617-9147","authenticated-orcid":false,"given":"Cinzia","family":"Forni","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"De Martino","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simone","family":"Beninati","sequence":"additional","affiliation":[{"name":"Department of Biology, University of Rome \u201cTor Vergata\u201d, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,7,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1479-7364-6-26","article-title":"The human crystallin gene families","volume":"6","author":"Wistow","year":"2012","journal-title":"Hum. 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