Glyceraldehyde 3-phosphate dehydrogenase activity in rat and human lenses and the fate of enzyme molecules in the aging lens

Dovrat, A.; Scharf, J; Gershon, David

doi:10.1016/0047-6374(84)90019-8

Cited by 32 publications

(18 citation statements)

References 7 publications

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“…The pronounced changes with age are unlikely to be due to the activity of lens enzymes. Although phospholipase activity has been observed in the whole lens, even at 60 years of age (Kamei 1996), several separate studies indicate that metabolic pathways are absent from the centre of adult human lenses (Dovrat and Gershon 1981;Dovrat et al 1984;Scharf et al 1987;Zhu et al 2010b). Fiber cells in the lens nucleus lack organelles and, since there is no protein turnover (Lynnerup et al 2008), it is likely that the enzymes which were active in the centre of young lenses have been denatured due to decades of exposure to body temperature.…”

Section: Discussionmentioning

confidence: 99%

Instability of the cellular lipidome with age

Hughes

Deeley

Blanksby

et al. 2011

AGE

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The human lens nucleus is formed in utero, and from birth onwards, there appears to be no significant turnover of intracellular proteins or membrane components. Since, in adults, this region also lacks active enzymes, it offers the opportunity to examine the intrinsic stability of macromolecules under physiological conditions. Fifty seven human lenses, ranging in age from 12 to 82 years, were dissected into nucleus and cortex, and the nuclear lipids analyzed by electrospray ionization tandem mass spectrometry. In the first four decades of life, glycerophospholipids (with the exception of lysophosphatidylethanolamines) declined rapidly, such that by age 40, their content became negligible. In contrast the level of ceramides and dihydroceramides, which were undetectable prior to age 30, increased approximately 100-fold. The concentration of sphingomyelins and dihydrosphingomyelins remained unchanged over the whole life span. As a consequence of this marked alteration in composition, the properties of fiber cell membranes in the centre of young lenses are likely to be very different from those in older lenses. Interestingly, the identification of age 40 years as a time of transition in the lipid composition of the nucleus coincides with previously reported macroscopic changes in lens properties (e.g., a massive age-related increase in lens stiffness) and related pathologies such as presbyopia. The underlying reasons for the dramatic change in the lipid profile of the human lens with age are not known, but are most likely linked to the stability of some membrane lipids in a physiological environment.

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Section: Discussionmentioning

confidence: 99%

Instability of the cellular lipidome with age

Hughes

Deeley

Blanksby

et al. 2011

AGE

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“…It is unlikely that any methyltransferase activity is available in the center of adult lenses, since enzymes appear to be denatured by decades of exposure to body temperature. 57,58 The regions of both gamma S and aA crystallin that were examined in this study are located in flexible regions of the native proteins. [59][60][61] Such parts appear to be more susceptible to the post-translational modifications of the type characterized here than Asp/Asn residues located within structured portions.…”

Section: Discussionmentioning

confidence: 99%

Racemization of Two Proteins over Our Lifespan: Deamidation of Asparagine 76 in γS Crystallin Is Greater in Cataract than in Normal Lenses across the Age Range

Hooi

Raftery

Truscott

2012

Invest. Ophthalmol. Vis. Sci.

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“…The barrier forms in the normal lens at middle age and uncouples the center of the lens from the metabolically active outer region. Because the lens grows continuously throughout life, the outmost part of the lens is the region that was formed most recently and has the highest concentration of active enzymes ( 7,8 ). It is where the major antioxidant glutathione (GSH) is synthesized and the oxidized form of glutathione rereduced ( 9, 10 ).…”

mentioning

confidence: 99%

Sphingolipid distribution changes with age in the human lens

Deeley

Hankin

Friedrich

et al. 2010

Journal of Lipid Research

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characterizing these can have clinical relevance for understanding the molecular basis of ocular conditions such as presbyopia ( 2 ) and nuclear cataract ( 3, 4 ).It is not known which are the critical factors predisposing the human lens to age-related nuclear (ARN) cataract. Research from one of us, over many years, suggests that the formation of an internal barrier to the diffusion of small molecules may be a key event in the onset of this pathology ( 5, 6 ). The barrier forms in the normal lens at middle age and uncouples the center of the lens from the metabolically active outer region. Because the lens grows continuously throughout life, the outmost part of the lens is the region that was formed most recently and has the highest concentration of active enzymes ( 7,8 ). It is where the major antioxidant glutathione (GSH) is synthesized and the oxidized form of glutathione rereduced ( 9, 10 ). Since GSH is essential for maintaining a reducing environment in the lens center and for protection of protein structure, formation of the barrier allows oxidative modifi cation of nuclear proteins that is the hallmark of nuclear cataract. The dimensions of the barrier region (7 mm equatorial × 3 mm axial) corresponds to the part of the adult lens that was synthesized immediately after birth ( 11,12 ).Recent data implicate the binding of denatured proteins to the fi ber cell membrane as the mechanism responsible for the barrier ( 13 ), possibly by occluding the membrane pores that normally facilitate the movement of GSH and water from cell to cell via connexon ( 14 ) and aquaporin 0 ( 15 ) channels, respectively. Moreover, aquaporin 0 requires interaction with distinct membrane lipids to form its correct functional conformation ( 15 ). If interactions with fi ber cell Abstract The formation of an internal barrier to the diffusion of small molecules in the lens during middle age is hypothesized to be a key event in the development of age-related nuclear (ARN) cataract. Changes in membrane lipids with age may be responsible. In this study, we investigated the effect of age on the distribution of sphingomyelins, the most abundant lens phospholipids. Human lens Due to a lack of turnover ( 1 ), the lens is an ideal tissue for examining age-related changes to biomolecules, and

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Glyceraldehyde 3-phosphate dehydrogenase activity in rat and human lenses and the fate of enzyme molecules in the aging lens

Cited by 32 publications

References 7 publications

Instability of the cellular lipidome with age

Instability of the cellular lipidome with age

Racemization of Two Proteins over Our Lifespan: Deamidation of Asparagine 76 in γS Crystallin Is Greater in Cataract than in Normal Lenses across the Age Range

Sphingolipid distribution changes with age in the human lens

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