Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro

Nandi, Sandip K.; Rankenberg, Johanna; Rakete, Stefan; Nahomi, Rooban B.; Glomb, Marcus A.; Linetsky, Mikhail; Nagaraj, Ram H.

doi:10.1007/s10719-020-09961-9

Cited by 2 publications

(1 citation statement)

References 46 publications

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“…The study did not report any serious adverse effect from use of EV-06, drug development had been abandoned following phase 2b clinical trial in which the drug did not achieve a statistically significant dose response. In addition, mercaptoethylguanidine could increase lens stiffness by preventing AGE formation in lens proteins and increasing lens glutathione levels ( 40 ). It is suggested that oxidative stress and AGE formation with age may promote lens hardening and cause presbyopia ( 11 ).…”

Section: Discussionmentioning

confidence: 99%

Hesperetin treatment attenuates glycation of lens proteins and advanced‑glycation end products generation

et al. 2023

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advanced glycation end products (aGes) in lens proteins increase with aging, thus inducing cataracts and/or presbyopia. Hesperetin (Hst), which is an abundant plant flavanone largely derived from citrus species, and its derivatives attenuate cataracts and presbyopia in vivo and in vitro; however, no reports have described its effects on aGe formation in lens proteins. The present study demonstrated that aGes in lens proteins increase with age in mice. additionally, it showed that Hst can prevent aGes and n(ε)-carboxymethyl-lysine generation and modification of lens proteins using in vitro in human lens epithelial cell lines and ex vivo in mouse lens organ cultures. Furthermore, treatment with Hst prevented lens hardening and decreased chaperone activity in lens proteins. These results suggested that Hst and its derivatives are good candidates for the prevention of presbyopia and cataracts.

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Section: Discussionmentioning

confidence: 99%

Hesperetin treatment attenuates glycation of lens proteins and advanced‑glycation end products generation

et al. 2023

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Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia

Panja

Gaikwad

Rankenberg

et al. 2023

IJMS

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With aging, human lenses lose the ability to focus on nearby objects due to decreases in accommodative ability, a condition known as presbyopia. An increase in stiffness or decrease in lens elasticity due to protein aggregation and insolubilization are the primary reasons for presbyopia. In this study, we tested aggrelyte-1 (S, N-diacetyl glutathione diethyl ester) for its ability to promote protein solubility and decrease the stiffness of lenses through its dual property of lysine acetylation and disulfide reduction. Treatment of water-insoluble proteins from aged human lenses (58–75 years) with aggrelyte-1 significantly increased the solubility of those proteins. A control compound that did not contain the S-acetyl group (aggrelyte-1C) was substantially less efficient in solubilizing water-insoluble proteins. Aggrelyte-1-treated solubilized protein had significant amounts of acetyllysine, as measured by Western blotting and LC-MS/MS. Aggrelytes increased the protein-free thiol content in the solubilized protein. Aged mouse (7 months) and human (44-66 years) lenses treated with aggrelyte-1 showed reduced stiffness accompanied by higher free thiol and acetyllysine levels compared with those treated with aggrelyte-1C or untreated controls. Our results suggested that aggrelyte-1 reduced lens stiffness through acetylation followed by disulfide reduction. This proof-of-concept study paves the way for developing aggrelyte-1 and related compounds to reverse presbyopia.

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Glycation-mediated protein crosslinking and stiffening in mouse lenses are inhibited by carboxitin in vitro

Cited by 2 publications

References 46 publications

Hesperetin treatment attenuates glycation of lens proteins and advanced‑glycation end products generation

Hesperetin treatment attenuates glycation of lens proteins and advanced‑glycation end products generation

Promotion of Protein Solubility and Reduction in Stiffness in Human Lenses by Aggrelyte-1: Implications for Reversing Presbyopia

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