Nucleotide levels in human lens: Regional distribution in different forms of senile cataract

Deußen, Andreas; Pau, Hans Wilhelm

doi:10.1016/0014-4835(89)90016-x

Cited by 16 publications

(14 citation statements)

References 15 publications

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“…However, no significant difference in the GTP level was noted between clear and cataractous lens, although GTP level seemed slightly depressed with advancing age (34). Our results show that GTP effectively inhibits the TGase-catalyzed protein cross-linking reaction, which is calcium-dependent.…”

Section: Discussionmentioning

confidence: 51%

Cell Type-specific Activation of Intracellular Transglutaminase 2 by Oxidative Stress or Ultraviolet Irradiation

Shin¹,

Jeon²,

Kim

et al. 2004

Journal of Biological Chemistry

104

102

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Transglutaminase (TGase) 2 is a ubiquitously expressed enzyme that modifies proteins by cross-linking or polyamination. An aberrant activity of TGase 2 has implicated its possible roles in a variety of diseases including age-related cataracts. However, the molecular mechanism by which TGase 2 is activated has not been elucidated. In this report, we showed that oxidative stress or UV irradiation elevates in situ TGase 2 activity. Neither the expression level nor the in vitro activity of TGase 2 appeared to correlate with the observed elevation of in situ TGase 2 activity. Screening a number of cell lines revealed that the level of TGase 2 activation depends on the cell type and also the environmental stress, suggesting that unrecognized cellular factor(s) may specifically regulate in situ TGase 2 activity. Concomitantly, we observed that human lens epithelial cells (HLE-B3) exhibited about 3-fold increase in in situ TGase 2 activity in response to the stresses. The activated TGase 2 catalyzed the formation of water-insoluble dimers or polymers of ␣B-crystallin, ␤B 2 -crystallin, and vimentin in HLE-B3 cells, providing evidence that TGase 2 may play a role in cataractogenesis. Thus, our findings indicate that in situ TGase 2 activity must be evaluated instead of in vitro activity to study the regulation mechanism and function of TGase 2 in biological and pathological processes.

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Section: Discussionmentioning

confidence: 51%

Cell Type-specific Activation of Intracellular Transglutaminase 2 by Oxidative Stress or Ultraviolet Irradiation

Shin¹,

Jeon²,

Kim

et al. 2004

Journal of Biological Chemistry

104

102

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“…In contrast, a loss of lactate dehydrogenase activity has already been detected histochemically in all cortical fibers in the early stages of subcapsular cataracts [3]. Regional distribution of adenine, guanidine and uridine (ATP, ADP, GTP and UTP) [4], and the content of glutathione [5], has been shown to be high in cortices of clear lenses and of cortical cataracts. These values were significantly less in cortices of subcapsular cataracts [3,4,5].…”

Section: Biochemical and Etiological Differencesmentioning

confidence: 99%

“…Regional distribution of adenine, guanidine and uridine (ATP, ADP, GTP and UTP) [4], and the content of glutathione [5], has been shown to be high in cortices of clear lenses and of cortical cataracts. These values were significantly less in cortices of subcapsular cataracts [3,4,5]. Human subcapsular cataracts but not cortical cataracts have also been found to be associated with activity loss in glutathione synthesis enzymes [6].…”

Section: Biochemical and Etiological Differencesmentioning

confidence: 99%

Cortical and Subcapsular Cataracts: Significance of Physical Forces

Pau¹

2005

Ophthalmologica

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Cortical cataracts usually begin with either sharp limited clear fluid clefts, resulting in opaque spokes, or clear lamellar separations, resulting in cuneiform opacities. They do not commence prior to 45 years of age. From this age on an increase in lens nuclei hardening can be detected. Therefore, during disaccommodation in older lenses, mechanical shear stresses must develop between the soft remaining cortices and the harder nuclei. These shear stresses are significant regarding the different cortical ruptures in predisposed lenses: in a privileged radial direction (according to zonular traction) of the sharp limited cortical spokes, or in parallel microridges at the commencement of lamellar separations, as observed when a rubber surface slides against a harder object. In pure cortical cataracts the ion pump (K⁺ > Na⁺) and investigated metabolic parameters remain largely intact. Therefore, it is not surprising that, in contrast to subcapsular cataracts, subcapsular opacities do not occur. Subcapsular cataracts are known to be caused by a variety of factors: aging, diabetes, corticosteroids, iridocyclitis, or X-ray, among many others. In contrast to cortical cataracts, subcapsular cataracts were found to be closely associated with ion pump damage (Na⁺ > K⁺) and a variety of metabolic activity alterations. In subcapsular cataracts passive fluids (from the vitreous and camera anterior) enter externally through the lens capsule. This initially forms numerous free clear, secondary grey, subcapsular fluid vacuoles. If the ion pump (metabolic barrier) is more severely damaged fluids may also enter the lens nucleus (secondary grey nuclear cataract), which rarely results in intumescent cataract. In cortical and subcapsular cataracts and lens perforations the main cause of grey opalescence appears to be the result of lens proteins (water-soluble crystalline) coming into direct contact with free fluids (water). In cortical cataracts this happens in the area of sharp limited mechanical cortical ruptures (fluid clefts), and in subcapsular cataracts during passive, external fluid entry, resulting in subcapsular fluid vacuoles and opacities, and also later grey-white nuclear opacities. The importance of water contact with water-soluble lens crystallines in behalf of light scattering and turbidness also has been investigated experimentally.

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“…These lenses were obtained 24-48 h following death and were used to quantify postmortem changes. As controls for the human lenses we used nucleotide levels of fresh clear lenses (n = 5), previously reported on [2]. The following lens fractions were studied: the anterior cortex plus epithelium (and capsule), the nucleus and the posterior cortex (and capsule).…”

Section: Methodsmentioning

confidence: 99%

“…Tissue levels of nucleotide phosphates in lens [1,2] amount to 20-25% of that found in heart muscle [3] or liver [1], With increasing age, global ATP levels in lenses from mouse, rab bit and bovine were shown to decrease [4,5]. In contrast, no significant age-dependent changes were reported in human lenses [6,7], In a study on regional nucleotide levels [2] we have recently shown that in the hu man lens cortex high levels of adenine, guanosine and uridine nucleotides are preserved even at advanced age. A marked decrease in lens nucleotide level was found exclusively in lenses which had developed a subcapsular cataract.…”

Section: Introductionmentioning

confidence: 99%

Nucleotide Levels in Human and Bovine Lenses: A Study on Regional postmortem Changes

Deußen

1990

Ophthalmic Res

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Regional lens adenine nucleotide levels were determined in human and bovine lenses using sensitive HPLC techniques. In adult lenses of both species adenine nucleotide levels were highest in the anterior cortex (plus epithelium and capsule) followed by the posterior cortex (plus capsule) and lowest in the nucleus. With increasing lens age ATP level remained steady in the anterior cortex (plus epithelium and capsule) and nucleus, while those in the posterior cortex showed a tendency toward decrease. In both species, human as well as bovine, adenine nucleotide levels of the anterior cortex (plus epithelium and capsule) underwent early postmortem changes. Thus, immediate postmortem sampling as well as regional determinations are a must for detailed studies of lens nucleotide metabolism.

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Nucleotide levels in human lens: Regional distribution in different forms of senile cataract

Cited by 16 publications

References 15 publications

Cell Type-specific Activation of Intracellular Transglutaminase 2 by Oxidative Stress or Ultraviolet Irradiation

Cell Type-specific Activation of Intracellular Transglutaminase 2 by Oxidative Stress or Ultraviolet Irradiation

Cortical and Subcapsular Cataracts: Significance of Physical Forces

Nucleotide Levels in Human and Bovine Lenses: A Study on Regional postmortem Changes

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