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Enzymatic antioxidative defence of erythrocytes in an Italian family with Hb Volga or α2β2 27 (B9) Ala → Asp
Clinic4 Chimicu Acta, 178 (1988) 345-348 Elsevier
345
CCA 04324
Letter to the Editor
Enzymatic antioxidative defence of erythrocytes in an Italian family tyith Hb Volga or arZ& 27 (B9) Ala -+ Asp Dear Editor, A case of moderately severe Heinz body hemolytic anemia in an Italian family [l] was associated with the presence in the carriers of Hb Volga, an unstable hemoglobin characterized by the substitution Ala + Asp at /?27(B9). According to the present view, the primary cause of hemolytic syndrome in carriers of Hb Volga is the increased instability of this hemoprotein, which is characterized by a higher rate of auto-oxidation and, therefore, by an increased free radical flux, which may induce damage to red cell membranes [2]. The hematological data for two patients under study (father and son, both heterozygotes for Hb Volga) indicate a different severity of hemolytic anemia; this has been attributed to the beneficial effect of splenectomy which was carried out only on the father [1,3]. The quantitative determination of the activity of the red blood cell enzymes (SOD, CAT and GPx) involved in controlling the steady state of oxygen radicals and repair mechanism in the erythrocyte membrane [4], has been examined. The activity of superoxide dismutase was similar for the two patients (father and son) and equal to the normal controls; on the other hand catalase activity was equally increased in both patients by approximately 40% as compared to the controls. The mechanism leading to an increased erythrocyte catalase activity in these patients is not clear, although a similar behavior has been reported in other cases with increased rate of hemoglobin oxidation [5-71. The glutathione peroxidase activity, is only slightly decreased for the son (this has been confirmed with blood samples obtained in different periods, and compared to different controls); it is well known that this is a key enzyme in providing protection against oxidative damage to red cell membrane [8], not only because it can metabolize H,O,, but especially because it can attack lipid peroxides. A complete set of data indicates that transferrin and ceruloplasmin, which are known to be the main plasma factors protecting lipids from peroxidation [9] are present in both patients at a level of 60-70% compared to control values (Table I). Other enzymatic activities connected with the red cell normal metabolism were found at normal values. 0009-8981/88/$03.50
0 1988 Elsevier Science Publishers
B.V. (Biomedical
Division)
I
* Spfenectomized.
Normal control
41.6 30.4
Father Son
*
Hct w
data
Relation
Hematological
TABLE
Hb
12.8 8.8
g/d]
4.73 3.28
RBC W/i
27S 26.8
Pg
88 93
MCH
MCV l/l
42 31
30.8 29.8
Relics %
MCHC g/d1
Heinz bodies
+“I-t-
1.8 4.4 0.16
mg/dl
Bilirubin
384
27x 282
mg/dl
mw’dl 99 Absent
Transferrin
Haptoglobin
74
49 45
nw’dl
Ceruloplasmin
37
31 24
mk3Jml
CSH in blood
4.20
5.04 8.00
ROOH in plasma nmol MDA/ml
341
In conclusion, because the Hb Volga content is the same in the RBCell for both patients, the more severe hemolytic syndrome in the son is mainly correlated to the presence of the spleen. However, the small decrease in GPx activity found in the son may be a contributing factor to account for the different severity of the hemolytic anemia between the two patients and parallel determinations before splenectomy may have been very instructive. Giancarlo Falcioni a Francesco Grelloni a Giampiero De Sanctis a Pa010 Pierani b Leonardo Felici b Giovanni Valentino Coppa b a Department of Cell Biology, University of Camerino, Camerino, Italy ’ Clinic of Pediatrics, University of Ancona, Ancona, Italy
References 1 Sciarrata GV, Ivaldi G, Sanson G, Wilson JB, Webber BB, Huisman THJ. Hb Volga or n2& 27(B9)Ala + Asp in an italian family. Hemoglobin 1985;9:91. 2 Carrel RW, Winterbom CC, Rachmilewitz EA. Activated oxygen and haemolysis. Br J Hematol 1975;30:259. 3 Kuis-Reerink JD, Jonxis JHP, Niazi GA, et al. Hb Volga or a& 27(B9)Ala Asp. An unstable hemoglobin variant in three generation of dutch family. Biochim Biophys Acta 1976;439:63. 4 Bozzi A, Mavelli I, Finazzi-Agrb A, et al. Enzyme defence against reactive oxygen derivatives. II. Erythrocytes and tumor cells. Mol Cell Biochem 1976;lO:ll. 5 Rachmilewitz EA, Lubin BH, Shoet SB. Lipids membrane peroxidation in thalassemia major. Blood 1976;47:495. 6 Fridaman MJ. In: Brewer GJ, ed. The red cell. Fifth Annual Arbor Conference. New York: Alan R. Liss, 1981;519. 7 Brooks J. The oxidation of hemoglobin to methemoglobin by oxygen. II. The relation between the rate of oxidation and the partial pressure of oxygen. Proc R Sot B London 1935;118:560. 8 Wendel A, William B. In: Jakoby, ed. Detoxication and drug metabolism: conjugation and related systems. Methods in Enzymol 1981;77:325. 9 Stoks J, Gutteridge JMC, Sharp RJ, Dormandy TL. The inhibition of lipid autoxidation by human serum and its relationship to serum proteins and alpha-tocopherol. Clin Sci Mol Med 1974;47:223.
Correspondence Italy.
to: G. Falcioni,
Department
of Cell Biology,
University
of Camerino,
62032 Camerino
345
CCA 04324
Letter to the Editor
Enzymatic antioxidative defence of erythrocytes in an Italian family tyith Hb Volga or arZ& 27 (B9) Ala -+ Asp Dear Editor, A case of moderately severe Heinz body hemolytic anemia in an Italian family [l] was associated with the presence in the carriers of Hb Volga, an unstable hemoglobin characterized by the substitution Ala + Asp at /?27(B9). According to the present view, the primary cause of hemolytic syndrome in carriers of Hb Volga is the increased instability of this hemoprotein, which is characterized by a higher rate of auto-oxidation and, therefore, by an increased free radical flux, which may induce damage to red cell membranes [2]. The hematological data for two patients under study (father and son, both heterozygotes for Hb Volga) indicate a different severity of hemolytic anemia; this has been attributed to the beneficial effect of splenectomy which was carried out only on the father [1,3]. The quantitative determination of the activity of the red blood cell enzymes (SOD, CAT and GPx) involved in controlling the steady state of oxygen radicals and repair mechanism in the erythrocyte membrane [4], has been examined. The activity of superoxide dismutase was similar for the two patients (father and son) and equal to the normal controls; on the other hand catalase activity was equally increased in both patients by approximately 40% as compared to the controls. The mechanism leading to an increased erythrocyte catalase activity in these patients is not clear, although a similar behavior has been reported in other cases with increased rate of hemoglobin oxidation [5-71. The glutathione peroxidase activity, is only slightly decreased for the son (this has been confirmed with blood samples obtained in different periods, and compared to different controls); it is well known that this is a key enzyme in providing protection against oxidative damage to red cell membrane [8], not only because it can metabolize H,O,, but especially because it can attack lipid peroxides. A complete set of data indicates that transferrin and ceruloplasmin, which are known to be the main plasma factors protecting lipids from peroxidation [9] are present in both patients at a level of 60-70% compared to control values (Table I). Other enzymatic activities connected with the red cell normal metabolism were found at normal values. 0009-8981/88/$03.50
0 1988 Elsevier Science Publishers
B.V. (Biomedical
Division)
I
* Spfenectomized.
Normal control
41.6 30.4
Father Son
*
Hct w
data
Relation
Hematological
TABLE
Hb
12.8 8.8
g/d]
4.73 3.28
RBC W/i
27S 26.8
Pg
88 93
MCH
MCV l/l
42 31
30.8 29.8
Relics %
MCHC g/d1
Heinz bodies
+“I-t-
1.8 4.4 0.16
mg/dl
Bilirubin
384
27x 282
mg/dl
mw’dl 99 Absent
Transferrin
Haptoglobin
74
49 45
nw’dl
Ceruloplasmin
37
31 24
mk3Jml
CSH in blood
4.20
5.04 8.00
ROOH in plasma nmol MDA/ml
341
In conclusion, because the Hb Volga content is the same in the RBCell for both patients, the more severe hemolytic syndrome in the son is mainly correlated to the presence of the spleen. However, the small decrease in GPx activity found in the son may be a contributing factor to account for the different severity of the hemolytic anemia between the two patients and parallel determinations before splenectomy may have been very instructive. Giancarlo Falcioni a Francesco Grelloni a Giampiero De Sanctis a Pa010 Pierani b Leonardo Felici b Giovanni Valentino Coppa b a Department of Cell Biology, University of Camerino, Camerino, Italy ’ Clinic of Pediatrics, University of Ancona, Ancona, Italy
References 1 Sciarrata GV, Ivaldi G, Sanson G, Wilson JB, Webber BB, Huisman THJ. Hb Volga or n2& 27(B9)Ala + Asp in an italian family. Hemoglobin 1985;9:91. 2 Carrel RW, Winterbom CC, Rachmilewitz EA. Activated oxygen and haemolysis. Br J Hematol 1975;30:259. 3 Kuis-Reerink JD, Jonxis JHP, Niazi GA, et al. Hb Volga or a& 27(B9)Ala Asp. An unstable hemoglobin variant in three generation of dutch family. Biochim Biophys Acta 1976;439:63. 4 Bozzi A, Mavelli I, Finazzi-Agrb A, et al. Enzyme defence against reactive oxygen derivatives. II. Erythrocytes and tumor cells. Mol Cell Biochem 1976;lO:ll. 5 Rachmilewitz EA, Lubin BH, Shoet SB. Lipids membrane peroxidation in thalassemia major. Blood 1976;47:495. 6 Fridaman MJ. In: Brewer GJ, ed. The red cell. Fifth Annual Arbor Conference. New York: Alan R. Liss, 1981;519. 7 Brooks J. The oxidation of hemoglobin to methemoglobin by oxygen. II. The relation between the rate of oxidation and the partial pressure of oxygen. Proc R Sot B London 1935;118:560. 8 Wendel A, William B. In: Jakoby, ed. Detoxication and drug metabolism: conjugation and related systems. Methods in Enzymol 1981;77:325. 9 Stoks J, Gutteridge JMC, Sharp RJ, Dormandy TL. The inhibition of lipid autoxidation by human serum and its relationship to serum proteins and alpha-tocopherol. Clin Sci Mol Med 1974;47:223.
Correspondence Italy.
to: G. Falcioni,
Department
of Cell Biology,
University
of Camerino,
62032 Camerino