Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis
Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis. Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated,...
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| Veröffentlicht in: | Kidney international 2001-02, Vol.59 (S78), p.S73-S76 |
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| creator | Galli, Francesco Beninati, Simone Benedetti, Serena Lentini, Alessandro Canestrari, Franco Tabilio, Antonio Buoncristiani, Umberto |
| description | Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis.
Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation.
Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD. the latter were tested for their effect on monouclear bone marrow cell proliferation.
In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 ± 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of > 100KD (peak 1) and of approximately 30 to 50 KD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E).
We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremictoxins contributing to the onset of the uremic anemia. |
| doi_str_mv | 10.1046/j.1523-1755.2001.59780073.x |
| format | Article |
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Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation.
Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD. the latter were tested for their effect on monouclear bone marrow cell proliferation.
In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 ± 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of > 100KD (peak 1) and of approximately 30 to 50 KD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E).
We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremictoxins contributing to the onset of the uremic anemia.</description><identifier>ISSN: 0085-2538</identifier><identifier>ISSN: 0098-6577</identifier><identifier>EISSN: 1523-1755</identifier><identifier>DOI: 10.1046/j.1523-1755.2001.59780073.x</identifier><identifier>PMID: 11168987</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Aged ; anemia ; Blood Proteins - chemistry ; Blood Proteins - toxicity ; CFU-E ; Colony-Forming Units Assay ; end-stage renal disease ; erythroid cells ; Erythropoiesis - drug effects ; Hematopoietic Stem Cells - drug effects ; hemodialysis ; Humans ; In Vitro Techniques ; Kidney Failure, Chronic - blood ; Kidney Failure, Chronic - therapy ; Macromolecular Substances ; Middle Aged ; Polyamines - blood ; Polyamines - chemistry ; Polyamines - toxicity ; Renal Dialysis ; spermidine ; Spermidine - blood ; Spermidine - chemistry ; Spermidine - toxicity ; Toxins, Biological - blood ; Toxins, Biological - toxicity ; Uremia - blood</subject><ispartof>Kidney international, 2001-02, Vol.59 (S78), p.S73-S76</ispartof><rights>2001 International Society of Nephrology</rights><rights>Copyright Nature Publishing Group Feb 2001</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-5f3a7df59e83731a1e37db6f2f276a10b06ecf371af4ac09ce74e518ef42fc5f3</citedby><cites>FETCH-LOGICAL-c459t-5f3a7df59e83731a1e37db6f2f276a10b06ecf371af4ac09ce74e518ef42fc5f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.proquest.com/docview/210112982?pq-origsite=primo$$EHTML$$P50$$Gproquest$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,64361,64365,72215</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11168987$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Galli, Francesco</creatorcontrib><creatorcontrib>Beninati, Simone</creatorcontrib><creatorcontrib>Benedetti, Serena</creatorcontrib><creatorcontrib>Lentini, Alessandro</creatorcontrib><creatorcontrib>Canestrari, Franco</creatorcontrib><creatorcontrib>Tabilio, Antonio</creatorcontrib><creatorcontrib>Buoncristiani, Umberto</creatorcontrib><title>Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis</title><title>Kidney international</title><addtitle>Kidney Int Suppl</addtitle><description>Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis.
Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation.
Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD. the latter were tested for their effect on monouclear bone marrow cell proliferation.
In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 ± 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of > 100KD (peak 1) and of approximately 30 to 50 KD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E).
We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremictoxins contributing to the onset of the uremic anemia.</description><subject>Aged</subject><subject>anemia</subject><subject>Blood Proteins - chemistry</subject><subject>Blood Proteins - toxicity</subject><subject>CFU-E</subject><subject>Colony-Forming Units Assay</subject><subject>end-stage renal disease</subject><subject>erythroid cells</subject><subject>Erythropoiesis - drug effects</subject><subject>Hematopoietic Stem Cells - drug effects</subject><subject>hemodialysis</subject><subject>Humans</subject><subject>In Vitro Techniques</subject><subject>Kidney Failure, Chronic - blood</subject><subject>Kidney Failure, Chronic - therapy</subject><subject>Macromolecular Substances</subject><subject>Middle Aged</subject><subject>Polyamines - blood</subject><subject>Polyamines - chemistry</subject><subject>Polyamines - toxicity</subject><subject>Renal Dialysis</subject><subject>spermidine</subject><subject>Spermidine - blood</subject><subject>Spermidine - chemistry</subject><subject>Spermidine - toxicity</subject><subject>Toxins, Biological - blood</subject><subject>Toxins, Biological - toxicity</subject><subject>Uremia - blood</subject><issn>0085-2538</issn><issn>0098-6577</issn><issn>1523-1755</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><recordid>eNqNkEFP3DAQha2qVVlo_0Jl0XOCx47jhJ4QooCERA_0WFleZ0wdbeKtndDdf49Xu8CV02hm3pun-Qj5DqwEVtVnfQmSiwKUlCVnDErZqoYxJcrNB7J43X0kC8YaWXApmiNynFLPct8K9pkcAUDdtI1akD-_wmo7YPSWrmOY0I_FOk_M4EekNoz9_GgmTOf0go74n9qVSYkGR-eIQ_ZMYePHRI1zaCc_PlKM2-lvDOvgMfn0hXxyZpXw66GekN8_rx4ub4q7--vby4u7wlaynQrphFGdky02QgkwgEJ1y9pxx1VtgC1ZjdYJBcZVxrLWoqpQQoOu4s5m9wk53d_NP_ybMU26D3Mcc6TmwAB42_As-rEX2RhSiuj0OvrBxK0Gpndkda939PSOnt6R1S9k9Sa7vx0i5uWA3Zv3gDILrvYCzI8-eYw6WY-jxc7HDEd3wb8r6Bl1kI07</recordid><startdate>20010201</startdate><enddate>20010201</enddate><creator>Galli, Francesco</creator><creator>Beninati, Simone</creator><creator>Benedetti, Serena</creator><creator>Lentini, Alessandro</creator><creator>Canestrari, Franco</creator><creator>Tabilio, Antonio</creator><creator>Buoncristiani, Umberto</creator><general>Elsevier Inc</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7QP</scope><scope>7RV</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>NAPCQ</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope></search><sort><creationdate>20010201</creationdate><title>Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis</title><author>Galli, Francesco ; 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Preliminary evidence on the accumulation of polyamine-protein conjugates (PPCs) was obtained in uremic patients. The presence of these substances in the plasma of hemodialysis (HD) patients was evaluated, and their possible contribution to uremic anemia was investigated by testing the effect of PPC synthesized in vitro on erythroid cell proliferation.
Plasma PPC was measured by high-performance liquid chromatography. The in vitro synthesis of PPC from human plasma was carried out by means of the enzyme transglutaminase in the presence of either [3H]-labeled or unlabeled spermidine (SPD). After gel filtration chromatography and detection of the fractions containing [3H]SPD. the latter were tested for their effect on monouclear bone marrow cell proliferation.
In three out of four patients examined, mainly SPD-protein conjugates (SPD-PC) were observed to accumulate during HD. The levels ranged from 0.17 to 4.93 pmol/mg proteins before dialysis, and these values increased at 30 minutes and at the end of the dialysis up to levels 11.90 pmol/mg. SPD-PC levels in healthy controls were 1.46 ± 0.82. SPD-PCs synthesized in vitro were recovered in two main fractions showing a molecular weight of > 100KD (peak 1) and of approximately 30 to 50 KD (peak 3), respectively. The SPD-PC contained in peak 1 showed the greatest inhibitory effect on colony-forming units-erythroid (CFU-E) proliferation without any appreciable effect on burst-forming units-erythroid (BFU-E).
We demonstrate that SPD-PC can accumulate in HD patients. These substances, which affect CFU-E proliferation, can be considered as an at yet unrevealed class of uremictoxins contributing to the onset of the uremic anemia.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11168987</pmid><doi>10.1046/j.1523-1755.2001.59780073.x</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Aged anemia Blood Proteins - chemistry Blood Proteins - toxicity CFU-E Colony-Forming Units Assay end-stage renal disease erythroid cells Erythropoiesis - drug effects Hematopoietic Stem Cells - drug effects hemodialysis Humans In Vitro Techniques Kidney Failure, Chronic - blood Kidney Failure, Chronic - therapy Macromolecular Substances Middle Aged Polyamines - blood Polyamines - chemistry Polyamines - toxicity Renal Dialysis spermidine Spermidine - blood Spermidine - chemistry Spermidine - toxicity Toxins, Biological - blood Toxins, Biological - toxicity Uremia - blood |
| title | Polymeric protein-polyamine conjugates: A new class of uremic toxins affecting erythropoiesis |
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