TY  - JOUR
AU  - Stojanović, Srđan Đ.
AU  - Stanić, Dragana
AU  - Nikolić, Milan
AU  - Raicevic, S
AU  - Spasić, Mihajlo B.
AU  - Niketic, V
PY  - 2005
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/713
AB  - The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD) tyrosine residue, which causes enzyme inactivation, is well established, This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO), conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous ill vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+) and nitroxyl (NO-) species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation ill vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels.
AB  - Dobro je poznato da peroksinitrit izaziva nitrovanje ostataka tirozina u mangan-superoksid- dismutazi (MnSOD) što dovodi do inaktivacije enzima. Pokazano je da nitrovanje i inaktivacija MnSOD-a nastaje u raznim bolestima za koje je karakteristič an oksidativni stres i povećana produkcija azot-monoksida (NO). Pošto se pri ovim uslovima očekuje nastajanje peroksinitrita predloženo je da peroksinitrit izaziva nitrovanje i inaktivaciju MnSOD in vivo. U našem prethodnom radu pokazali smo da MnSOD katalizuje transformaciju NO u nitrozonijum (NO+) i nitroksil (NO–) reaktivne vrste, te identifikovali neke od modifikacija molekula enzima koje pri tome nastaju izazivajući njegovu inaktivaciju. U ovom radu je pokazano da pri izlaganju MnSOD azot-monoksidu dolazi i do nitrovanja ostatka tirozina u molekulu enzima, što doprinosi njegovoj inaktivaciji. Ovi rezultati ukazuju da pri interakciji MnSOD sa NO dolazi do nastajanja nitrujućih vrsta, što baca novo svetlo na proces nitrovanja ostataka tirozina i inaktivaciju MnSOD in vivo. Ovo može da predstavlja novi mehanizam kojim MnSOD štiti ćeliju odštetnih efekata izazvanih hiperprodukcijom azot-monoksida. Međutim ekstenzivne modifikacije i inaktivacija MnSOD do kojih dolazi pri produženom izlaganju enzima NO, uvećaće toksične efekte izazvane povećanim koncentracijama superoksida i NO u ćeliji.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration
T1  - Mangan-superoksid-dismutaza (MnSOD) katalizuje NO-zavisno nitrovanje ostatka tirozina
VL  - 70
IS  - 4
SP  - 601
EP  - 608
DO  - 10.2298/JSC0504601S
ER  - 

@article{
author = "Stojanović, Srđan Đ. and Stanić, Dragana and Nikolić, Milan and Raicevic, S and Spasić, Mihajlo B. and Niketic, V",
year = "2005",
abstract = "The peroxynitrite-induced nitration of manganese superoxide dismutase (MnSOD) tyrosine residue, which causes enzyme inactivation, is well established, This led to suggestions that MnSOD nitration and inactivation in vivo, detected in various diseases associated with oxidative stress and overproduction of nitric monoxide (NO), conditions which favor peroxynitrite formation, is also caused by peroxynitrite. However, our previous ill vitro study demonstrated that exposure of MnSOD to NO led to NO conversion into nitrosonium (NO+) and nitroxyl (NO-) species, which caused enzyme modifications and inactivation. Here it is reported that MnSOD is tyrosine nitrated upon exposure to NO, as well as that MnSOD nitration contributes to inactivation of the enzyme. Collectively, these observations provide a compelling argument supporting the generation of nitrating species in MnSOD exposed to NO and shed a new light on MnSOD tyrosine nitration and inactivation ill vivo. This may represent a novel mechanism by which MnSOD protects cell from deleterious effects associated with overproduction of NO. However, extensive MnSOD modification and inactivation associated with prolonged exposure to NO will amplify the toxic effects caused by increased cell superoxide and NO levels., Dobro je poznato da peroksinitrit izaziva nitrovanje ostataka tirozina u mangan-superoksid- dismutazi (MnSOD) što dovodi do inaktivacije enzima. Pokazano je da nitrovanje i inaktivacija MnSOD-a nastaje u raznim bolestima za koje je karakteristič an oksidativni stres i povećana produkcija azot-monoksida (NO). Pošto se pri ovim uslovima očekuje nastajanje peroksinitrita predloženo je da peroksinitrit izaziva nitrovanje i inaktivaciju MnSOD in vivo. U našem prethodnom radu pokazali smo da MnSOD katalizuje transformaciju NO u nitrozonijum (NO+) i nitroksil (NO–) reaktivne vrste, te identifikovali neke od modifikacija molekula enzima koje pri tome nastaju izazivajući njegovu inaktivaciju. U ovom radu je pokazano da pri izlaganju MnSOD azot-monoksidu dolazi i do nitrovanja ostatka tirozina u molekulu enzima, što doprinosi njegovoj inaktivaciji. Ovi rezultati ukazuju da pri interakciji MnSOD sa NO dolazi do nastajanja nitrujućih vrsta, što baca novo svetlo na proces nitrovanja ostataka tirozina i inaktivaciju MnSOD in vivo. Ovo može da predstavlja novi mehanizam kojim MnSOD štiti ćeliju odštetnih efekata izazvanih hiperprodukcijom azot-monoksida. Međutim ekstenzivne modifikacije i inaktivacija MnSOD do kojih dolazi pri produženom izlaganju enzima NO, uvećaće toksične efekte izazvane povećanim koncentracijama superoksida i NO u ćeliji.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration, Mangan-superoksid-dismutaza (MnSOD) katalizuje NO-zavisno nitrovanje ostatka tirozina",
volume = "70",
number = "4",
pages = "601-608",
doi = "10.2298/JSC0504601S"
}

Stojanović, S. Đ., Stanić, D., Nikolić, M., Raicevic, S., Spasić, M. B.,& Niketic, V.. (2005). Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 70(4), 601-608.
https://doi.org/10.2298/JSC0504601S

Stojanović SĐ, Stanić D, Nikolić M, Raicevic S, Spasić MB, Niketic V. Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration. in Journal of the Serbian Chemical Society. 2005;70(4):601-608.
doi:10.2298/JSC0504601S .

Stojanović, Srđan Đ., Stanić, Dragana, Nikolić, Milan, Raicevic, S, Spasić, Mihajlo B., Niketic, V, "Manganese superoxide dismutase (MnSOD) catalyzes NO-dependent tyrosine residue nitration" in Journal of the Serbian Chemical Society, 70, no. 4 (2005):601-608,
https://doi.org/10.2298/JSC0504601S . .

TY  - JOUR
AU  - Stojanović, Srđan Đ.
AU  - Stanić, Dragana
AU  - Nikolić, Milan
AU  - Spasić, Mihajlo B.
AU  - Niketic, V
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/675
AB  - The conversion of NO into its congeners, nitrosonium (NO+) and nitroxyl (HNO/NO-) species, has important consequences in NO metabolism. Dinitrosyl iron complex (DNIC) combined with thiol ligands was shown to catalyze the conversion of NO into NO+, resulting in the synthesis of S-nitrosothiols (RSNO) both in vitro and in vivo. The formation mechanism of DNIC was proposed to involve the intermediate release of nitroxyl. Since the detection of hydroxylamine (as the product of a rapid reaction of HNO/NO- with thiols) is taken as the evidence for nitroxyl generation, we examined the formation of hydroxylamine, RSNO, and nitrite (the product of a rapid reaction of NO+ with water) in neutral solutions containing iron ions and thiols exposed to NO under anaerobic conditions. Hydroxylamine was detected in NO treated solutions of iron ions in the presence of cysteine, but not glutathione (GSH). The addition of urate, a major "free" iron-binding agent in humans, to solutions of GSH and iron ions, and the subsequent treatment of these solutions with NO increased the synthesis of GSNO and resulted in the formation of hydroxylamine. This caused a loss of urate and yielded a novel nitrosative/nitration product. GSH attenuated the urate decomposition to such a degree that it could be reflected as the function of GSH:urate. Results described here contribute to the understanding of the role of iron ions in catalyzing the conversion of NO into HNO/NO- and point to the role of uric acid not previously described. (C) 2004 Elsevier Inc. All rights reserved.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Nitric Oxide: Biology and Chemistry
T1  - Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species
VL  - 11
IS  - 3
SP  - 256
EP  - 262
DO  - 10.1016/j.niox.2004.09.007
ER  - 

@article{
author = "Stojanović, Srđan Đ. and Stanić, Dragana and Nikolić, Milan and Spasić, Mihajlo B. and Niketic, V",
year = "2004",
abstract = "The conversion of NO into its congeners, nitrosonium (NO+) and nitroxyl (HNO/NO-) species, has important consequences in NO metabolism. Dinitrosyl iron complex (DNIC) combined with thiol ligands was shown to catalyze the conversion of NO into NO+, resulting in the synthesis of S-nitrosothiols (RSNO) both in vitro and in vivo. The formation mechanism of DNIC was proposed to involve the intermediate release of nitroxyl. Since the detection of hydroxylamine (as the product of a rapid reaction of HNO/NO- with thiols) is taken as the evidence for nitroxyl generation, we examined the formation of hydroxylamine, RSNO, and nitrite (the product of a rapid reaction of NO+ with water) in neutral solutions containing iron ions and thiols exposed to NO under anaerobic conditions. Hydroxylamine was detected in NO treated solutions of iron ions in the presence of cysteine, but not glutathione (GSH). The addition of urate, a major "free" iron-binding agent in humans, to solutions of GSH and iron ions, and the subsequent treatment of these solutions with NO increased the synthesis of GSNO and resulted in the formation of hydroxylamine. This caused a loss of urate and yielded a novel nitrosative/nitration product. GSH attenuated the urate decomposition to such a degree that it could be reflected as the function of GSH:urate. Results described here contribute to the understanding of the role of iron ions in catalyzing the conversion of NO into HNO/NO- and point to the role of uric acid not previously described. (C) 2004 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Nitric Oxide: Biology and Chemistry",
title = "Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species",
volume = "11",
number = "3",
pages = "256-262",
doi = "10.1016/j.niox.2004.09.007"
}

Stojanović, S. Đ., Stanić, D., Nikolić, M., Spasić, M. B.,& Niketic, V.. (2004). Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species. in Nitric Oxide: Biology and Chemistry
Academic Press Inc Elsevier Science, San Diego., 11(3), 256-262.
https://doi.org/10.1016/j.niox.2004.09.007

Stojanović SĐ, Stanić D, Nikolić M, Spasić MB, Niketic V. Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species. in Nitric Oxide: Biology and Chemistry. 2004;11(3):256-262.
doi:10.1016/j.niox.2004.09.007 .

Stojanović, Srđan Đ., Stanić, Dragana, Nikolić, Milan, Spasić, Mihajlo B., Niketic, V, "Iron catalyzed conversion of NO into nitrosonium (NO+) and nitroxyl (HNO/NO-) species" in Nitric Oxide: Biology and Chemistry, 11, no. 3 (2004):256-262,
https://doi.org/10.1016/j.niox.2004.09.007 . .

TY  - JOUR
AU  - Nikolić, Milan
AU  - Stanić, Dragana
AU  - Antonijevic, N
AU  - Niketic, V
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/165
AB  - Objective: To study lipid fraction that is occasionally observed in red blood cell (RBC) hemolysate (supernatants from which membranes were separated). Study design: Plasma lipid profiles, cholesterol (Ch) and phospholipids (PL) in intact RBCs, RBC membranes and hemolysates were examined in young healthy male population in winter and summer. Results: The RBC Ch and PL content was significantly higher than in membranes, both in winter and summer. The "excess" of cholesterol (associated with phospholipid) was bound to hemoglobin yielding Hb-lipid adduct (Hb-Ch), the pools in the RBC membrane remaining virtually unaltered. Levels of hemoglobin- lipid complex (Hb-Ch), which were significantly higher in winter than in summer (30% and 19% of the total Hb, respectively), positively correlated with plasma HDL cholesterol levels. Conclusion: To our knowledge, this is the first demonstration of cholesterol binding to Hb. The results suggest influence of plasma lipoprotein metabolism on the formation of Hb-Ch. (C) 2003 The Canadian Society of Clinical Chemists. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Clinical Biochemistry
T1  - Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation?
VL  - 37
IS  - 1
SP  - 22
EP  - 26
DO  - 10.1016/j.clinbiochem.2003.10.002
ER  - 

@article{
author = "Nikolić, Milan and Stanić, Dragana and Antonijevic, N and Niketic, V",
year = "2004",
abstract = "Objective: To study lipid fraction that is occasionally observed in red blood cell (RBC) hemolysate (supernatants from which membranes were separated). Study design: Plasma lipid profiles, cholesterol (Ch) and phospholipids (PL) in intact RBCs, RBC membranes and hemolysates were examined in young healthy male population in winter and summer. Results: The RBC Ch and PL content was significantly higher than in membranes, both in winter and summer. The "excess" of cholesterol (associated with phospholipid) was bound to hemoglobin yielding Hb-lipid adduct (Hb-Ch), the pools in the RBC membrane remaining virtually unaltered. Levels of hemoglobin- lipid complex (Hb-Ch), which were significantly higher in winter than in summer (30% and 19% of the total Hb, respectively), positively correlated with plasma HDL cholesterol levels. Conclusion: To our knowledge, this is the first demonstration of cholesterol binding to Hb. The results suggest influence of plasma lipoprotein metabolism on the formation of Hb-Ch. (C) 2003 The Canadian Society of Clinical Chemists. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Clinical Biochemistry",
title = "Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation?",
volume = "37",
number = "1",
pages = "22-26",
doi = "10.1016/j.clinbiochem.2003.10.002"
}

Nikolić, M., Stanić, D., Antonijevic, N.,& Niketic, V.. (2004). Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation?. in Clinical Biochemistry
Pergamon-Elsevier Science Ltd, Oxford., 37(1), 22-26.
https://doi.org/10.1016/j.clinbiochem.2003.10.002

Nikolić M, Stanić D, Antonijevic N, Niketic V. Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation?. in Clinical Biochemistry. 2004;37(1):22-26.
doi:10.1016/j.clinbiochem.2003.10.002 .

Nikolić, Milan, Stanić, Dragana, Antonijevic, N, Niketic, V, "Cholesterol bound to hemoglobin in normal human erythrocytes: a new form of cholesterol in circulation?" in Clinical Biochemistry, 37, no. 1 (2004):22-26,
https://doi.org/10.1016/j.clinbiochem.2003.10.002 . .

TY  - JOUR
AU  - Stanić, Dragana
AU  - Nikolić, Milan
AU  - Niketic, V
PY  - 2004
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/638
AB  - Recently, it was demonstrated that prolonged hyperinsulinism associated with hypoglycemia, both in vivo and in vitro, caused covalent glycoinositolphospholipid (GPI) binding to the C termini of both hemoglobin beta-chains, which resulted in the formation of a novel, hitherto unrecognized, minor hemoglobin fraction (GPI-Hb) (Niketic et al. Biochem. Biophys. Res. Commun. 239 (1997)435). In this study, it was demonstrated that exposure of erythrocyte membranes to insulin causes the activation of membrane protease as well as that the formation of GPI-Hb parallels its activity. It is suggested that the insulin-activated protease is able to catalyze. albeit slowly, the transpeptidation, i.e., the replacement of the carboxy-terminal amino acid(s) residues of the Hb beta-chains with GPI as an exogenous nucleophile. To our knowledge the present results show for the first time that insulin stimulates protease activity in erythrocyte membranes, as well as that insulin-activated protease may be involved in post-translational GPI binding to proteins.
AB  - U našim ranijim radovima pokazano je da u uslovima hiperinsulinizma i hipoglikemije, in vivo i in vitro, dolazi do kovalentnog vezivanja glikoinozitolfosfolipida (GPI) za karboksilne krajeve oba β-niza molekula hemoglobina (Hb), što se manifestuje nastajanjem nove, do tada nepoznate, manje frakcije hemoglobina (GPI-Hb) (Niketić et al., Biochem. Biophys. Res. Commun. 239 (1997) 435). U ovom radu je pokazano da vezivanje insulina za membrane eritrocita izaziva aktiviranje membranske proteaze, te da je nastajanje GPI-Hb u korelaciji sa proteaznom aktivnošću. Pretpostavljeno je da proteaza aktivirana insulinom može, mada sporo, da katalizuje reakciju transpeptidacije, tj. zamenu aminokiselinskih ostataka sa karboksilnog kraja β-nizova molekula Hb sa GPI-lipidom kao egzogenim nukleofilom. Prema našem saznanju opisani rezultati prvi puta pokazuju da insulin stimuliše proteaznu aktivnost u eritrocitima, te da je ova aktivnost povezana sa post-translacionim vezivanjem GPI-lipida za proteine.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Covalent glycoinositolphospholipid (GPI) binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease
T1  - Kovalentno vezivanje glikoinozitolfosfolipida (GPI) za hemoglobin pod dejstvom insulina praćeno je aktiviranjem proteaze iz membrane eritrocita
VL  - 69
IS  - 5
SP  - 343
EP  - 348
DO  - 10.2298/JSC0405343S
ER  - 

@article{
author = "Stanić, Dragana and Nikolić, Milan and Niketic, V",
year = "2004",
abstract = "Recently, it was demonstrated that prolonged hyperinsulinism associated with hypoglycemia, both in vivo and in vitro, caused covalent glycoinositolphospholipid (GPI) binding to the C termini of both hemoglobin beta-chains, which resulted in the formation of a novel, hitherto unrecognized, minor hemoglobin fraction (GPI-Hb) (Niketic et al. Biochem. Biophys. Res. Commun. 239 (1997)435). In this study, it was demonstrated that exposure of erythrocyte membranes to insulin causes the activation of membrane protease as well as that the formation of GPI-Hb parallels its activity. It is suggested that the insulin-activated protease is able to catalyze. albeit slowly, the transpeptidation, i.e., the replacement of the carboxy-terminal amino acid(s) residues of the Hb beta-chains with GPI as an exogenous nucleophile. To our knowledge the present results show for the first time that insulin stimulates protease activity in erythrocyte membranes, as well as that insulin-activated protease may be involved in post-translational GPI binding to proteins., U našim ranijim radovima pokazano je da u uslovima hiperinsulinizma i hipoglikemije, in vivo i in vitro, dolazi do kovalentnog vezivanja glikoinozitolfosfolipida (GPI) za karboksilne krajeve oba β-niza molekula hemoglobina (Hb), što se manifestuje nastajanjem nove, do tada nepoznate, manje frakcije hemoglobina (GPI-Hb) (Niketić et al., Biochem. Biophys. Res. Commun. 239 (1997) 435). U ovom radu je pokazano da vezivanje insulina za membrane eritrocita izaziva aktiviranje membranske proteaze, te da je nastajanje GPI-Hb u korelaciji sa proteaznom aktivnošću. Pretpostavljeno je da proteaza aktivirana insulinom može, mada sporo, da katalizuje reakciju transpeptidacije, tj. zamenu aminokiselinskih ostataka sa karboksilnog kraja β-nizova molekula Hb sa GPI-lipidom kao egzogenim nukleofilom. Prema našem saznanju opisani rezultati prvi puta pokazuju da insulin stimuliše proteaznu aktivnost u eritrocitima, te da je ova aktivnost povezana sa post-translacionim vezivanjem GPI-lipida za proteine.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Covalent glycoinositolphospholipid (GPI) binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease, Kovalentno vezivanje glikoinozitolfosfolipida (GPI) za hemoglobin pod dejstvom insulina praćeno je aktiviranjem proteaze iz membrane eritrocita",
volume = "69",
number = "5",
pages = "343-348",
doi = "10.2298/JSC0405343S"
}

Stanić, D., Nikolić, M.,& Niketic, V.. (2004). Covalent glycoinositolphospholipid (GPI) binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 69(5), 343-348.
https://doi.org/10.2298/JSC0405343S

Stanić D, Nikolić M, Niketic V. Covalent glycoinositolphospholipid (GPI) binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease. in Journal of the Serbian Chemical Society. 2004;69(5):343-348.
doi:10.2298/JSC0405343S .

Stanić, Dragana, Nikolić, Milan, Niketic, V, "Covalent glycoinositolphospholipid (GPI) binding to hemoglobin is associated with insulin-activation of erythrocyte membrane protease" in Journal of the Serbian Chemical Society, 69, no. 5 (2004):343-348,
https://doi.org/10.2298/JSC0405343S . .

TY  - JOUR
AU  - Tomasevic, N
AU  - Nikolić, Milan
AU  - Klappe, K
AU  - Hoekstra, D
AU  - Niketic, V
PY  - 2003
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/536
AB  - Under hypoglycemic conditions, concomitant hyperinsulinism causes an apparent modification of hemoglobin (Hb) which is manifested by its a aggregation (Niketic et al.. Clin. Chim. Acia 197 (1991) 47). In the present work the causes and mechanisms underlying this Hb modification were Studied. Hemoglobin isolated from normal erythrocytes incubated with insulin was analyzed by applying P-31-spectrometry and lipid extraction and analysis. To study the dynamics of the plasma membrane during hperinsulinisra a fluorescent lipid-analog was applied. In the presence of insulin phosphatidylserine (PS). phosphatidylethanolamine (PE) and cholesterol were found to bind to Hb. Lipid binding resulted in Hb aggregation, a condition that can be reproduced when phospholipids arc incubated with Hb in vitro. Using a fluorescent lipid-analog, it was also shown that exposing crythrocytes to supraphysiological concentrations of insulin in vitro resulted in the internalization of lipids. The results presented in this work, may have relevance to cases of diabetes mellitus and hypoglycemia.
AB  - Uranijim radovima je pokazano da hiperinsulinizam u uslovima hipoglikemije izaziva modifikaciju molekula hemoglobina koja se manifestuje njegovim agregiranjem (Niketić et al., Clin. Chim. Acta 197 (1991) 47). U ovom radu ispitivana je ova modifikacija molekula hemoglobina, kao i mehanizam njenog nastajanja. Primenom 31P-spektrometrije i analizom lipidnog ekstrakta utvrđeno je da u normalnim eritrocitima inkubiranim sa insulinom dolazi do vezivanja fosfatidil-serina, fosfatidil-etanolmina i holesterola za molekul hemoglobina. Vezivanje fosfolipida za hemoglobin dovodi do njegovog agregiranja što je potvrđeno eksperimentima u kojima je hemoglobin inkubiran sa fosfolipidima in vitro. Primenom fluorescentnog lipidnog analoga pokazano je da pri izlaganju eritrocita suprafiziološkim koncentracijama insulina dolazi do internalizacije membranskih lipida. Dobijeni rezultati mogu biti od značaja za pacijente obolele od šećerne bolesti i hipoglikemije.
PB  - Serbian Chemical Soc, Belgrade
T2  - Journal of the Serbian Chemical Society
T1  - Insulin-induced lipid binding to hemoglobin
T1  - Vezivanje lipida za hemoglobin pod dejstvom insulina
VL  - 68
IS  - 1
SP  - 25
EP  - 33
DO  - 10.2298/JSC0301025T
ER  - 

@article{
author = "Tomasevic, N and Nikolić, Milan and Klappe, K and Hoekstra, D and Niketic, V",
year = "2003",
abstract = "Under hypoglycemic conditions, concomitant hyperinsulinism causes an apparent modification of hemoglobin (Hb) which is manifested by its a aggregation (Niketic et al.. Clin. Chim. Acia 197 (1991) 47). In the present work the causes and mechanisms underlying this Hb modification were Studied. Hemoglobin isolated from normal erythrocytes incubated with insulin was analyzed by applying P-31-spectrometry and lipid extraction and analysis. To study the dynamics of the plasma membrane during hperinsulinisra a fluorescent lipid-analog was applied. In the presence of insulin phosphatidylserine (PS). phosphatidylethanolamine (PE) and cholesterol were found to bind to Hb. Lipid binding resulted in Hb aggregation, a condition that can be reproduced when phospholipids arc incubated with Hb in vitro. Using a fluorescent lipid-analog, it was also shown that exposing crythrocytes to supraphysiological concentrations of insulin in vitro resulted in the internalization of lipids. The results presented in this work, may have relevance to cases of diabetes mellitus and hypoglycemia., Uranijim radovima je pokazano da hiperinsulinizam u uslovima hipoglikemije izaziva modifikaciju molekula hemoglobina koja se manifestuje njegovim agregiranjem (Niketić et al., Clin. Chim. Acta 197 (1991) 47). U ovom radu ispitivana je ova modifikacija molekula hemoglobina, kao i mehanizam njenog nastajanja. Primenom 31P-spektrometrije i analizom lipidnog ekstrakta utvrđeno je da u normalnim eritrocitima inkubiranim sa insulinom dolazi do vezivanja fosfatidil-serina, fosfatidil-etanolmina i holesterola za molekul hemoglobina. Vezivanje fosfolipida za hemoglobin dovodi do njegovog agregiranja što je potvrđeno eksperimentima u kojima je hemoglobin inkubiran sa fosfolipidima in vitro. Primenom fluorescentnog lipidnog analoga pokazano je da pri izlaganju eritrocita suprafiziološkim koncentracijama insulina dolazi do internalizacije membranskih lipida. Dobijeni rezultati mogu biti od značaja za pacijente obolele od šećerne bolesti i hipoglikemije.",
publisher = "Serbian Chemical Soc, Belgrade",
journal = "Journal of the Serbian Chemical Society",
title = "Insulin-induced lipid binding to hemoglobin, Vezivanje lipida za hemoglobin pod dejstvom insulina",
volume = "68",
number = "1",
pages = "25-33",
doi = "10.2298/JSC0301025T"
}

Tomasevic, N., Nikolić, M., Klappe, K., Hoekstra, D.,& Niketic, V.. (2003). Insulin-induced lipid binding to hemoglobin. in Journal of the Serbian Chemical Society
Serbian Chemical Soc, Belgrade., 68(1), 25-33.
https://doi.org/10.2298/JSC0301025T

Tomasevic N, Nikolić M, Klappe K, Hoekstra D, Niketic V. Insulin-induced lipid binding to hemoglobin. in Journal of the Serbian Chemical Society. 2003;68(1):25-33.
doi:10.2298/JSC0301025T .

Tomasevic, N, Nikolić, Milan, Klappe, K, Hoekstra, D, Niketic, V, "Insulin-induced lipid binding to hemoglobin" in Journal of the Serbian Chemical Society, 68, no. 1 (2003):25-33,
https://doi.org/10.2298/JSC0301025T . .

TY  - JOUR
AU  - Niketic, V
AU  - Tomasevic, N
AU  - Nikolić, Milan
PY  - 1997
UR  - https://cherry.chem.bg.ac.rs/handle/123456789/2599
AB  - In this work a novel hitherto unrecognised minor hemoglobin (Hb) fraction, which we detected previously in hemolysates of erythrocytes exposed to a high concentration of insulin under hypoglycemic conditions, both in vivo and in vitro, is analysed. The modification of Hb in HbA1x was shown to be due the addition of glycoinositolphospholipid (GPI) to the C termini of both beta polypeptide chains. A structurally related minor Hb fraction was identified in erythrocytes exposed in vitro to insulin-mimetic agent, trypsin. To our knowledge this is the first demonstration of such a modification of Hb, as well as the first demonstration of post-translational GPI binding to proteins in response to insulin. The mechanism proposed for GPI-Hb formation is briefly described. (C) 1997 Academic Press.
PB  - Academic Press Inc Jnl-Comp Subscriptions, San Diego
T2  - Biochemical and Biophysical Research Communications
T1  - Covalent glycoinositolphospholipid binding to hemoglobin: A new post-translational modification of hb occurring in hyperinsulinism with concomitant hypoglycemia
VL  - 239
IS  - 2
SP  - 435
EP  - 438
DO  - 10.1006/bbrc.1997.7362
ER  - 

@article{
author = "Niketic, V and Tomasevic, N and Nikolić, Milan",
year = "1997",
abstract = "In this work a novel hitherto unrecognised minor hemoglobin (Hb) fraction, which we detected previously in hemolysates of erythrocytes exposed to a high concentration of insulin under hypoglycemic conditions, both in vivo and in vitro, is analysed. The modification of Hb in HbA1x was shown to be due the addition of glycoinositolphospholipid (GPI) to the C termini of both beta polypeptide chains. A structurally related minor Hb fraction was identified in erythrocytes exposed in vitro to insulin-mimetic agent, trypsin. To our knowledge this is the first demonstration of such a modification of Hb, as well as the first demonstration of post-translational GPI binding to proteins in response to insulin. The mechanism proposed for GPI-Hb formation is briefly described. (C) 1997 Academic Press.",
publisher = "Academic Press Inc Jnl-Comp Subscriptions, San Diego",
journal = "Biochemical and Biophysical Research Communications",
title = "Covalent glycoinositolphospholipid binding to hemoglobin: A new post-translational modification of hb occurring in hyperinsulinism with concomitant hypoglycemia",
volume = "239",
number = "2",
pages = "435-438",
doi = "10.1006/bbrc.1997.7362"
}

Niketic, V., Tomasevic, N.,& Nikolić, M.. (1997). Covalent glycoinositolphospholipid binding to hemoglobin: A new post-translational modification of hb occurring in hyperinsulinism with concomitant hypoglycemia. in Biochemical and Biophysical Research Communications
Academic Press Inc Jnl-Comp Subscriptions, San Diego., 239(2), 435-438.
https://doi.org/10.1006/bbrc.1997.7362

Niketic V, Tomasevic N, Nikolić M. Covalent glycoinositolphospholipid binding to hemoglobin: A new post-translational modification of hb occurring in hyperinsulinism with concomitant hypoglycemia. in Biochemical and Biophysical Research Communications. 1997;239(2):435-438.
doi:10.1006/bbrc.1997.7362 .

Niketic, V, Tomasevic, N, Nikolić, Milan, "Covalent glycoinositolphospholipid binding to hemoglobin: A new post-translational modification of hb occurring in hyperinsulinism with concomitant hypoglycemia" in Biochemical and Biophysical Research Communications, 239, no. 2 (1997):435-438,
https://doi.org/10.1006/bbrc.1997.7362 . .