Oxidation of Goat Hepatic Galectin-1 Induces Change in Secondary Structure

Pande, Abhay H.; Gupta, Rajesh Kumar; Sumati,; Hajela, Krishnan

doi:10.2174/0929866033478960

Cited by 12 publications

(11 citation statements)

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“…In contrast, our protein contained both monomeric and dimeric fractions. Similar to that observed with native protein, its protective effects were inhibited by galactose and its CD spectrum was similar to that report to the native reduced form of the protein (Pande et al, 2003). In order to bind galactose, galectin-1 must be in a dimeric form.…”

Section: Discussionsupporting

confidence: 85%

Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression

Lekishvili

Hesketh

Brazier

et al. 2006

Eur J of Neuroscience

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One of the major causes of neuronal death in neurodegenerative disease is excitotoxicity from the neurotransmitter glutamate. This form of cell death could arise from either excess levels of glutamate due to decreased astrocyte clearance or due to increased susceptibility. We have identified galectin-1, a galactose-binding lectin, as a potential neuroprotective factor secreted by astrocytes. Our results show that both native and recombinant galectin-1 protects mouse and rat cerebellar neurons from the toxic effects of glutamate. Galectin-1 applied to neurons increased their expression of the NMDA receptor NR1 and increased the proportion of the NR1a subunit subtype while antisense knockdown of the NR1a receptor blocked the neuroprotective effect of galectin-1. This effect of the protein was dependent upon it carbohydrate recognition domain, suggesting that the protein acts in a reduced dimerized form. In addition, galectin-1 caused a decreased expression of PKC associated with increased resistance to glutamate toxicity. These results suggest that the astrocytic lectin galectin-1 could protect neurons against the effects of excitotoxicity as seen in stroke and ischemic injury.

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Section: Discussionsupporting

confidence: 85%

Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression

Lekishvili

Hesketh

Brazier

et al. 2006

Eur J of Neuroscience

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“…Previous studies demonstrated that following oxidation, each subunit of Gal-1 forms three discrete intramolecular disulfide bridges (13,14). Disulfide bridge formation results in a significant conformational change (20,47,48), which prohibits ligand recognition and prevents dimerization (13). Crystallographic studies strongly suggest impaired conformational rotation of Cys residues during dimerization (49 -51).…”

Section: Discussionmentioning

confidence: 99%

Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation

Stowell

Cho

Feasley

et al. 2009

Journal of Biological Chemistry

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Galectin-1 (Gal-1) regulates leukocyte turnover by inducing the cell surface exposure of phosphatidylserine (PS), a ligand that targets cells for phagocytic removal, in the absence of apoptosis. Gal-1 monomer-dimer equilibrium appears to modulate Gal-1-induced PS exposure, although the mechanism underlying this regulation remains unclear. Here we show that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidation. A mutant form of Gal-1, containing C2S and V5D mutations (mGal-1), exhibits impaired dimerization and fails to induce cell surface PS exposure while retaining the ability to recognize carbohydrates and signal Ca 2؉ flux in leukocytes. mGal-1 also displayed enhanced sensitivity to oxidation, whereas ligand, which partially protected Gal-1 from oxidation, enhanced Gal-1 dimerization. Continual incubation of leukocytes with Gal-1 resulted in gradual oxidative inactivation with concomitant loss of cell surface PS, whereas rapid oxidation prevented mGal-1 from inducing PS exposure. Stabilization of Gal-1 or mGal-1 with iodoacetamide fully protected Gal-1 and mGal-1 from oxidation. Alkylation-induced stabilization allowed Gal-1 to signal sustained PS exposure in leukocytes and mGal-1 to signal both Ca 2؉ flux and PS exposure. Taken together, these results demonstrate that monomer-dimer equilibrium regulates Gal-1 sensitivity to oxidative inactivation and provides a mechanism whereby ligand partially protects Gal-1 from oxidation.Immunological homeostasis relies on efficient contraction of activated leukocytes following an inflammatory episode. Several factors, including members of the galectin and tumor necrosis factor families (1, 2), regulate leukocyte turnover by inducing apoptotic cell death. In contrast, several galectin family members, in particular galectin-1 (Gal-1), 2 uniquely regulate neutrophil turnover by inducing phosphatidylserine (PS) exposure, which normally sensitizes apoptotic cells to phagocytic removal (3, 4), independent of apoptosis, a process recently termed preaparesis (5).Previous studies suggested that dimerization may be required for Gal-1-induced PS exposure, as a mutant form of Gal-1 (mGal-1) containing two point mutations within the dimer interface, C2S and V5D (C2S,V5D), displays impaired Gal-1 dimerization and fails to induce PS exposure (6). However, the manner in which monomer-dimer equilibrium regulates Gal-1 signaling remains unclear. Previous studies suggest that dimerization may be required for efficient cross-linking of functional receptors or the formation of signaling lattices (7-9). Consistent with this, monomeric mutants of several other galectins fail to induce PS exposure or signal leukocytes (4, 8). Gal-1 signaling of PS exposure requires initial signaling events, such as mobilization of intracellular Ca 2ϩ followed by sustained receptor engagement (10). Although mGal-1 fails to induce PS exposure (6), whether mGal-1 can induce these initial signaling events remains unknown (10).In addition to directly regulating signaling, monomer-dimer equilibrium may ...

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“…Galectin‐1 from sheep liver and goat liver was isolated as described previously [13] and identity of the purified protein with galectin‐1 was confirmed by amino acid sequencing of a partial trypsin digest [14]. In order to maintain galectin‐1 activity in non‐reducing environment, batches of carboxyamidomethylated galectin‐1 (cam‐galectin‐1) were regularly prepared by reacting the galectin with 25 mM iodoacetamide at 4 °C for 8 h in Tris/HCl buffer (pH 7.5) containing 150 mM NaCl and 5 mM β‐mercaptoethanol in the presence of lactose [15].…”

Section: Methodsmentioning

confidence: 99%

Carbohydrate‐induced modulation of cell membrane. VIII. Agglutination with mammalian lectin galectin‐1 increases osmofragility and membrane fluidity of trypsinized erythrocytes

et al. 2006

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Interaction of lectins with cell surface determinants may alter membrane properties. Using trypsinized rabbit erythrocytes as model we tested the capacity of an endogenous lectin in this respect. Galectin-1 is a member of an adhesion/growthregulatory family known to interact for example with ganglioside GM 1 and also the hydrophobic tail of oncogenic H-Ras. Assays on membrane fluidity and osmofragility detect galectin-1's capacity to increase the parameters. Moreover, it increases susceptibility of erythrocytes to radical damage. These observations indicate the potential of this endogenous lectin to affect membrane properties beyond the immediate interaction with cell surface epitopes.

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Oxidation of Goat Hepatic Galectin-1 Induces Change in Secondary Structure

Cited by 12 publications

References 0 publications

Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression

Mouse galectin‐1 inhibits the toxicity of glutamate by modifying NR1 NMDA receptor expression

Ligand Reduces Galectin-1 Sensitivity to Oxidative Inactivation by Enhancing Dimer Formation

Carbohydrate‐induced modulation of cell membrane. VIII. Agglutination with mammalian lectin galectin‐1 increases osmofragility and membrane fluidity of trypsinized erythrocytes

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