Mechanism of spectrin degradation induced by phenylhydrazine in intact human erythrocytes

Arduini, Arduino; Storto, Stefano; Belfiglio, Maurizio; Sourti, Rosa; Mancinelli, Giovanna; Federici, Giorgio

doi:10.1016/0005-2736(89)90515-4

Cited by 25 publications

(8 citation statements)

References 37 publications

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“…Colocalization of autoantibodies with band 3 tetramers observed in in vitro phenylhydrazine-stressed erythrocytes [149] did not have to be due to band 3 aggregation; usually, protein aggregation is a final out come of other denaturational changes so per haps the antibodies recognized altered con formation rather than altered oligomeric state of band 3. Moreover, it has been dem onstrated recently that phenylhydrazine in duces a direct breakdown of membrane pro teins [155] and oxidatively damaged pro teins have been shown to be selectively de graded in erythrocytes [156][157][158]. It cannot be excluded, therefore, that antibodies to trapped band 3 degradation fragments con tributed to the observed coclustering of au tologous IgG with oxidatively induced band 3 aggregates.…”

Section: Formation O F 'Senescent Cell Antigen' During Red Cell Agingmentioning

confidence: 99%

Erythrocyte Aging: Physical and Chemical Membrane Changes

Bartosz¹

1991

Gerontology

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The mammalian erythrocyte is an interesting model for studies of membrane aging. Experimental approaches to this problem involve, first of all, comparison of properties of erythrocytes separated by density because red blood cell age correlates with density in principle. Other approaches to study red cell membrane aging, such as hypertransfusion, are also discussed. A number of physical and chemical changes occur in erythrocytes with aging. Crucial to the elucidation of aging mechanisms is to determine which are primary and which are secondary. Immunoglobulin G binding triggers cellular removal and seems necessary for the recognition of senescent erythrocytes. Cellular deformability decreases while fragility to hemolytic factors generally increases and surface charge density does not alter. Perhaps more important are reactions of reactive oxygen species with membrane constituents and subsequent proteolysis. These are implicated as causative factors in red cell aging, immunoglobulin binding and recognition of senescent erythrocytes.

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Section: Formation O F 'Senescent Cell Antigen' During Red Cell Agingmentioning

confidence: 99%

Erythrocyte Aging: Physical and Chemical Membrane Changes

Bartosz¹

1991

Gerontology

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“…Exposure of erythrocytes to PHZ results in the degradation of both monomers of spectrin, a major cytoskeleton membrane protein (27). These results implicated oxidation products of PHZ and not proteolytic degradation as major contributors to PHZ-induced protein damage in red blood cells ghosts (28).…”

Section: Physiological Parameters (Mean ϯ Standard Deviation) Of Wementioning

confidence: 87%

“…It might also cause BAEP abnormalities by directly displacing bilirubin from albumin, or by producing free radicals, which have been shown to degrade serum albumin (28) and spectrin (27,28), and could result in increased free bilirubin. However, these are unlikely because the TB levels in blood rose dramatically, and when bilirubin is not bound to albumin, it exits the blood stream almost completely within half an hour (15).…”

Section: Physiological Parameters (Mean ϯ Standard Deviation) Of Wementioning

confidence: 99%

A New Animal Model of Hemolytic Hyperbilirubinemia-Induced Bilirubin Encephalopathy (Kernicterus)

Rice

Shapiro

2008

Pediatr Res

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Neonatal hyperbilirubinemia can cause bilirubin encephalopathy (kernicterus). Spontaneously jaundiced (jj) Gunn rats treated with sulfonamide (sulfa) to displace bilirubin from serum albumin, develop bilirubin encephalopathy and abnormal brainstem auditory evoked potentials (BAEPs) comparable with human newborns. We hypothesized phenylhydrazine (PHZ)-induced hemolysis would significantly elevate total plasma bilirubin (TB) in jj Gunn rat pups and produce BAEP abnormalities similar to those observed after sulfa. PHZ 0, 25, 50, or 75 mg/kg was administered intraperitonealy

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“…The proposed mechanism of PH induced hemolysis involves increased oxidative stress in erythrocyte membrane caused by i) peroxidation of membrane lipids as a result of auto-oxidation of PH and interaction of oxygen radicals with membrane lipids, ii) generation of superoxide anion radical by PH and formation of Heinz bodies, iii) enhanced levels of hydrogen peroxide in erythrocytes resulting in glutathione depletion and iv) production of aryl, hydroxyl, superoxide, and phenyl radicals by PH [4, 14, 15, 21, 34 ]. The mechanism of PH induced hemolysis also involves rupturing of erythrocyte membrane due to binding of PH with the membrane proteins such as spectrin with a ligand derived from its aryl portion [1]. PH is also known to degrade hemoglobin by direct oxidation of oxyhemoglobin to methemoglobin [26].…”

Section: Discussionmentioning

confidence: 99%

Optimization of phenylhydrazine induced hyperbilirubinemia in experimental rabbit

2016

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Induction of hyperbilirubinemia in experimental rabbits by phenylhydrazine was optimized in terms of dose, dose interval and number of doses using response surface methodology. Central Composite Design was employed using five levels for each of the three input variables. Degree of hyperbilirubinemia was measured in terms of bilirubin level in serum of animals. A dose dependent significant elevation (P<0.05) of total serum bilirubin level was observed which was optimized by using eight factorial, six axial and six central points as suggested by experimental design. Optimum levels of phenylhydrazine dose, total number of doses and a dose interval to achieve maximum elevation (4.06 mg/dl−1) of total serum bilirubin were found to be 11.56 mg/kg−1 body weight, 8 and 24.65 h, respectively. The induction procedure was validated by performing five replicate experiments on a group of five animals which showed 3.56 ± 0.47 mg/kg−1 body weight elevation in total serum bilirubin level.

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Mechanism of spectrin degradation induced by phenylhydrazine in intact human erythrocytes

Cited by 25 publications

References 37 publications

Erythrocyte Aging: Physical and Chemical Membrane Changes

Erythrocyte Aging: Physical and Chemical Membrane Changes

A New Animal Model of Hemolytic Hyperbilirubinemia-Induced Bilirubin Encephalopathy (Kernicterus)

Optimization of phenylhydrazine induced hyperbilirubinemia in experimental rabbit

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