Dataset Information

Age-related cleavages of crystallins in human lens cortical fibre cells generate a plethora of low molecular weight peptides and cross-linked crystallin complexes

ABSTRACT: A large variety of low molecular weight (LMW) peptides, derived from the breakdown of crystallins, have been reported in middle to old age human lenses. The proliferation of these LMW peptides coincides with the earliest stages of cataract formation, suggesting that the protein cleavages involved may contribute to the aggregation and insolubilisation of crystallins – these being hall marks of cataractogenesis. This study reports the identification of 238 endogenous LMW crystallin peptides from the cortical extracts of human lenses aged 16, 44, 75 and 83 years. Analysis of the peptide terminal amino acids showed that Lys and Arg were situated at the C-terminus with significantly higher frequency compared to other residues, suggesting that trypsin-like proteolysis may be active in the lens cortical fibre cells. Selected reaction monitoring (SRM) analysis of a prominent αA-crystallin peptide (αA57-65) showed that the concentration of this peptide in the human lens increased gradually to middle age, after which the rate of αA57-65 formation escalated significantly. Using 2-D gel electrophoresis and nanoLC-ESI-MS/MS, 13 protein complexes of 40-150 kDa consisting of multiple crystallin components were characterised from the water soluble cortical extracts of an adult human lens. The detection of these protein complexes suggested the possibility of crystallin cross-linking, with these complexes potentially acting to stabilise degraded crystallins by sequestration into water soluble complexes.

INSTRUMENT(S): QSTAR

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Bile

DISEASE(S): Disease Free

SUBMITTER: Xiaomin Song

LAB HEAD: Xiaomin Song

PROVIDER: PXD001593 | Pride | 2016-09-29

REPOSITORIES: Pride

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			Action	DRS
	75CWI-US_1apr10.wiff	Wiff
	75CWI-US_1apr10.wiff.1.idx2	Wiff
	75CWI-US_1apr10undigested (F059900).mzid_75CWI-US_1apr10undigested_(F059900).pride.mgf.gz	Mzid
	75CWI-US_1apr10undigested (F059900).pride.mztab.gz	Mztab
	75CWI-US_1apr10undigestedF059900.mzid.gz	Mzid

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Age-related cleavages of crystallins in human lens cortical fiber cells generate a plethora of endogenous peptides and high molecular weight complexes.

Su Shih-Ping SP Song Xiaomin X Xavier Dylan D Aquilina J Andrew JA

Proteins 20150819 10

Low molecular weight peptides derived from the breakdown of crystallins have been reported in adult human lenses. The proliferation of these LMW peptides coincides with the earliest stages of cataract formation, suggesting that the protein cleavages involved may contribute to the aggregation and insolubilization of crystallins. This study reports the identification of 238 endogenous LMW crystallin peptides from the cortical extracts of four human lenses representing young, middle and old-age hum ...[more]

PMID: 26238763

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