Oxidative Stress and Age-Related Cataract

Ottonello, Simone; Foroni, Chiara; Carta, Arturo; Petrucco, Stefania; Maraini, G

doi:10.1159/000027474

Cited by 126 publications

(70 citation statements)

References 26 publications

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“…After additional 5 h of growth, the bacterial cells were harvested by centrifugation at 9,000 ϫ g for 10 min. The same procedure was used for the expression of uniformly 15 N-enriched CRBP, except that the bacteria were grown in M9 minimal medium containing 15 NH 4 Cl (Cambridge Isotope Laboratories, Andover, MA) as the sole nitrogen source.…”

Section: Methodsmentioning

confidence: 99%

“…The role of the carrier in efficient retinyl-ester synthesis has been confirmed by an in vivo study (14). For the metabolic utilization of vitamin A, apoCRBP promotes retinyl-ester hydrolysis and binds the released retinol (15). CRBP-delivered retinol is converted to retinaldehyde by an enzyme located on the cytosolic side of endoplasmic reticulum, which was first isolated from the microsomal fraction of rat liver (16,17).…”

mentioning

confidence: 92%

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Structure and Backbone Dynamics of Apo- and Holo-cellular Retinol-binding Protein in Solution

Franzoni¹,

Lücke²,

Pérez³

et al. 2002

Journal of Biological Chemistry

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Retinoid-binding proteins play an important role in regulating transport, storage, and metabolism of vitamin A and its derivatives. The solution structure and backbone dynamics of rat cellular retinol-binding protein type I (CRBP) in the apo-and holo-form have been determined and compared using multidimensional high resolution NMR spectroscopy. The global fold of the protein is consistent with the common motif described for members of the intracellular lipid-binding protein family. The most relevant difference between the NMR structure ensembles of apo-and holoCRBP is the higher backbone disorder, in the ligand-free form, of some segments that frame the putative entrance to the ligandbinding site. These comprise ␣-helix II, the subsequent linker to ␤-strand B, the hairpin turn between ␤-strands C and D, and the ␤E-␤F turn. The internal backbone dynamics, obtained from 15 N relaxation data (T 1 , T 2 , and heteronuclear nuclear Overhauser effect) at two different fields, indicate several regions with significantly higher backbone mobility in the apoprotein, including the ␤C-␤D and ␤E-␤F turns. Although apoCRBP contains a binding cavity more shielded than that of any other retinoid carrier, conformational flexibility in the portal region may assist retinol uptake. The stiffening of the backbone in the holoprotein guarantees the stability of the complex during retinol transport and suggests that targeted retinol release requires a transiently open state that is likely to be promoted by the acceptor or the local environment.Vitamin A derivatives play important roles in a variety of biological processes including vision, cell growth, cell differentiation, and morphogenesis (1). Plasma transport of retinol to target cells and intracellular transport for either storage or metabolic conversion are performed by binding proteins that belong to the calycin superfamily. The cytosolic carriers are members of the intracellular lipid-binding protein (i-LBP) 1 family, characterized by molecular masses of around 15 kDa. Their structure consists of a 10-stranded ␤-barrel, formed by two orthogonal ␤-sheets, and two short ␣-helices (2). The two best known intracellular carriers of retinol are cellular retinolbinding protein type I (CRBP), widely distributed in various tissues (3, 4), and cellular retinol-binding protein type II (CRBP-II), present in the enterocytes of the small intestine and in neonatal hepatocytes (5, 6). The structures of rat apo-and holoCRBP-II have been solved both in the crystal (7) and in solution (8, 9), whereas the only structure of CRBP available to date was that of the holoprotein in the crystal (10). More recently, two other retinol carriers have been identified as follows: murine CRBP-III, expressed primarily in heart, muscle, and adipose tissue (11); and human CRBP-III, most abundant in liver and kidney, whose structure in the retinol-free form has been solved by x-ray crystallography (12).In the cell, the poorly water-soluble retinol is stored within membranes as a retinyl-ester derivative of long-cha...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 92%

Structure and Backbone Dynamics of Apo- and Holo-cellular Retinol-binding Protein in Solution

Franzoni¹,

Lücke²,

Pérez³

et al. 2002

Journal of Biological Chemistry

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“…It is well established that oxidative stress, which refers to the cellular damage caused by oxygen radicals, is the major contributor to cataractogenesis [2][3][4]. Oxidative stress plays a significant role in the degradation, oxidation, crosslinking and aggregation of lens proteins, and also triggers the lens epithelial cell apoptosis, which is regarded as the common molecular basis of the initiation and subsequent progression of cataract [5][6].…”

Section: Introductionmentioning

confidence: 99%

Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

et al. 2007

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The apoptosis of lens epithelial cells has been proposed as the common basis of cataract formation, with oxidative stress as the major cause. This study was performed to investigate the protective effect of the herbal constituent parthenolide against oxidative stress-induced apoptosis of human lens epithelial (HLE) cells and the possible molecular mechanisms involved. HLE cells (SRA01-04) were incubated with 50 µM H 2 O 2 in the absence or presence of different doses of parthenolide (10, 20 and 50 µM). To study apoptosis, the cells were assessed by morphologic examination and Annexin V-propidium iodide double staining flow cytometry; to investigate the underlying molecular mechanisms, the expression of caspase-3 and caspase-9 were assayed by Western blot and quantitative RT-PCR, and the activities of caspase-3 and caspase-9 were measured by a Chemicon caspase colorimetric activity assay kit. Stimulated with H 2 O 2 for 18 h, a high fraction of HLE cells underwent apoptosis, while in the presence of parthenolide of different concentrations, dose-dependent blocking of HLE cell apoptosis was observed. The expression of caspase-3 and caspase-9 induced by H 2 O 2 in HLE cells was significantly reduced by parthenolide both at the protein and mRNA levels, and the activation of caspase-3 and caspase-9 was also suppressed by parthenolide in a dose-dependent manner. In conclusion, parthenolide prevents HLE cells from oxidative stress-induced apoptosis through inhibition of the activation of caspase-3 and caspase-9, suggesting a potential protective effect against cataract formation.

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“…A number of studies have provided evidence for an important role of CRBPs in vitamin A homeostasis. Specifically, in vitro studies have suggested that CRBP I is involved in retinol internalization and intercellular transfer (10 -12), retinol esterification (13)(14)(15), retinyl ester hydrolysis (10,16), and the oxidation of retinol to retinaldehyde, a key step of retinoic acid biosynthesis (17,18). A recent in vivo study has shown that retinol esterification and intercellular retinol transfer between liver cells are strongly impaired in CRBP I-null mice, suggesting a key role of CRBP I in these two processes (19).…”

mentioning

confidence: 99%

Ligand Binding and Structural Analysis of a Human Putative Cellular Retinol-binding Protein

Folli¹,

Calderone²,

Ramazzina³

et al. 2002

Journal of Biological Chemistry

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Three cellular retinol-binding protein (CRBP) types (CRBP I, II, and III) with distinct tissue distributions and retinoid binding properties have been structurally characterized thus far. A human binding protein, whose mRNA is expressed primarily in kidney, heart, and transverse colon, is shown here to be a CRBP family member (human CRBP IV), according to amino acid sequence, phylogenetic analysis, gene structure organization, and x-ray structural analysis. Retinol binding to CRBP IV leads to an absorption spectrum distinct from a typical holo-CRBP spectrum and is characterized by an affinity (K d ‫؍‬ ϳ200 nM) lower than those for CRBP I, II, and III, as established in direct and competitive binding assays. As revealed by mutagenic analysis, the presence in CRBP IV of His 108 in place of Gln 108 is not responsible for the unusual holo-CRBP IV spectrum. The 2-Å resolution crystal structure of human apo-CRBP IV is very similar to those of other structurally characterized CRBPs. The side chain of Tyr 60 is present within the binding cavity of the apoprotein and might affect the interaction with the retinol molecule. These results indicate that human CRBP IV belongs to a clearly distinct CRBP subfamily and suggest a relatively different mode of retinol binding for this binding protein.

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Oxidative Stress and Age-Related Cataract

Cited by 126 publications

References 26 publications

Structure and Backbone Dynamics of Apo- and Holo-cellular Retinol-binding Protein in Solution

Structure and Backbone Dynamics of Apo- and Holo-cellular Retinol-binding Protein in Solution

Parthenolide protects human lens epithelial cells from oxidative stress-induced apoptosis via inhibition of activation of caspase-3 and caspase-9

Ligand Binding and Structural Analysis of a Human Putative Cellular Retinol-binding Protein

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