4.5 Article

Acceleration of age-induced proteolysis in the guinea pig lens nucleus by in vivo exposure to hyperbaric oxygen: A mass spectrometry analysis

期刊

EXPERIMENTAL EYE RESEARCH
卷 210, 期 -, 页码 -

出版社

ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exer.2021.108697

关键词

Aquaporin-0; Mass spectrometry; Alpha crystallin; Protein truncation; Lens; Hyperbaric oxygen; Nuclear cataract; alpha A66-80 peptide

资金

  1. NIH [EY02027, EY013462, EY024258, EY008126]

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Research has shown that hyperbaric oxygen treatment accelerates the aging process of the lens in guinea pigs, leading to the development of nuclear cataracts. This treatment results in truncation of proteins such as aquaporin-0 and alpha A-crystallin, mirroring observations in age-related cataracts in humans.
Hyperbaric oxygen (HBO) treatment of animals or ocular lenses in culture recapitulates many molecular changes observed in human age-related nuclear cataract. The guinea pig HBO model has been one of the best examples of such treatment leading to dose-dependent development of lens nuclear opacities. In this study, complimentary mass spectrometry methods were employed to examine protein truncation after HBO treatment of aged guinea pigs. Quantitative liquid chromatography-mass spectrometry (LC-MS) analysis of the membrane fraction of guinea pig lenses showed statistically significant increases in aquaporin-0 (AQP0) C-terminal truncation, consistent with previous reports of accelerated loss of membrane and cytoskeletal proteins. In addition, imaging mass spectrometry (IMS) analysis spatially mapped the acceleration of age-related alpha A-crystallin truncation in the lens nucleus. The truncation sites in alpha A-crystallin closely match those observed in human lenses with age. Taken together, our results suggest that HBO accelerates the normal lens aging process and leads to nuclear cataract.

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