ReferenceID 2880
Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed β H-Crystallins Polymerization in Calcium-Induced Experimental Cataract
Int J Mol Sci
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)-ca
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Record Fields
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- Reference Id
- 2880
- Evidence Id
- 19470
- Core Evidence Id
- 19470
- Source Reference Id
- 5745
- Herb2 Reference Id
- HBREF006542
- Subject Paper Key
- HBIN044493_32751462
- Pubmed Id
- 32751462
- Doi
- 10.3390/ijms21155427
- Paper Title
- Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed β H-Crystallins Polymerization in Calcium-Induced Experimental Cataract
- Paper Abstract
- 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(gamma-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 betaH-crystallins and in particular to the betaB2- and mostly in betaB3-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(gamma-glutamyl) SPD, the protein-bound N8-mono(gamma-glutamyl) SPD was found the mainly available derivative for the potential formation of betaB3-crystallins cross-links by protein-bound N1-N8-bis(gamma-glutamyl)SPD. In conclusion, FAD-PAO degradation of the N8-terminal reactive residue of the crystallins bound N1-mono(gamma-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(gamma-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.
- Journal
- Int J Mol Sci
- Publish Year
- 2020
- Experiment Subject
- rabbit
- Experiment Type
- Animal Experiment
- Phenotype Related
- Senile Cataract; Cataract
- Paper Title Cn
- Paper Title En
- Polyamine Oxidase Is Involved in Spermidine Reduction of Transglutaminase Type 2-Catalyzed β H-Crystallins Polymerization in Calcium-Induced Experimental Cataract
- Bilingual Status
- semi_complete