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Nguyen, John Van,

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Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa /

Record Type:	Electronic resources : Monograph/item
Title/Author:	Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa // John Van Nguyen.
Author:	Nguyen, John Van,
Description:	1 electronic resource (153 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 66-11, Section: B.
Contained By:	Dissertations Abstracts International66-11B.
Subject:	Pharmacology. -
Online resource:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3161022
ISBN:	9780496943555

Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa /
Nguyen, John Van,

Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa /John Van Nguyen. - 1 electronic resource (153 pages)

Source: Dissertations Abstracts International, Volume: 66-11, Section: B.

The aim of our study was to extend our understanding of polyamine metabolism by investigating how eukaryotes and prokaryotes metabolically process exogenous polyamines. A new series of polyamines, the aminopolyamines, were first assembled. Their metabolic profiles and impact on cellular and bacterial growth were measured. These newly synthesized aminopolyamines were screened in both eukaryotic and prokaryotic models. In the eukaryotic model, the murine leukemia L1210 cells were exposed to each aminopolyamine, and the 48-h and 96-h IC50 values were measured (in addition to their effect on polyamine metabolism). In the prokaryotic model, P. aeruginosa was used to study the impact of the synthetic aminopolyamines on its growth and polyamine metabolism. Studies in L1210 cells revealed that 2-aminoputrescine (2-NH2-PUT), and 6-aminospermine (6-NH2-SPM) had no significant impact on cellular growth with 48-h IC50 values >100 μM; while 7-aminospermidine (7-NH2-SPD) had a very moderate effect with a 48-h IC50 of 60 μM and a 96-h IC50 of 9 μM. The aminopolyamine N1,N8-diethyl-7-aminospermidine (7-NH2-DESPD) also showed a mild effect on cellular growth with a 48-h IC50 of 100 μM and a 96-h IC50 of 6 μM. At a concentration of 1 μM, 7-NH2-SPD and 7-NH2-DESPD had a slight impact on ODC by reducing the enzymatic activity to 72% and 79% of control, respectively. The aminopolyamine 6-NH2-SPM was more active by reducing ODC activity to 52% of control. In addition, 6-NH 2-SPM reduced AdoMetDC activity to 70% of control. While 7-NH2 -SPD and 6-NH2-SPM did not significantly stimulate spermidine/spermine- N1-acetyltranslerase (SSAT), 7-NH2-DESPD showed a moderate SSAT stimulation by upregulating SSAT to 303% of control. L1210 cells were able to catabolically convert 7-NH2-SPD to 2-NH 2-PUT and biosynthesize 6-NH2-SPM from 7-NH2-SPD. Besides, when exposed to 6-NH2-SPM, these cells converted this aminopolyamine to 7-NH2-SPD, and then to 2-NH2-PUT. When exposed to 7-NH2-DESPD or 6-NH2-DESPM, deethylation of these diethylated aminopolyamines also occurred inside the L1210 cell, possibly via the SSAT/PAO pathway. In P. aeruginosa, 2-OH-PUT and 7-OH-SPD are not produced endogenously. However, when exposed to 2-OH-PUT, the bacteria elaborated 2-OH-PUT into 7-OH-SPD. A similar scenario occurred in which 2-NH2-PUT was converted to 7-NH2-SPD by P. aeruginosa. This bacterium was incapable of producing 6-NH2-SPM from 7-NH2 -SPD. However, when exposed to 6-NH2-SPM, it was able to metabolize 6-NH2-SPM to 7-NH2-SPD and 2-NH2-PUT. Our results in this dissertation significantly add to the understanding of how various polyamine analogues are metabolically processed in both eukaryotes and prokaryotes.

English

ISBN: 9780496943555Subjects--Topical Terms:

634543
Pharmacology.
Subjects--Index Terms:

Aminopolyamines

Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa /
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245 1 0 $a Syntheses and metabolic profiles of aminopolyamines in the murine leukemia L1210 cell and the pathogenic bacterium Pseudomonas aeruginosa / $c John Van Nguyen.
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520 $a The aim of our study was to extend our understanding of polyamine metabolism by investigating how eukaryotes and prokaryotes metabolically process exogenous polyamines. A new series of polyamines, the aminopolyamines, were first assembled. Their metabolic profiles and impact on cellular and bacterial growth were measured. These newly synthesized aminopolyamines were screened in both eukaryotic and prokaryotic models. In the eukaryotic model, the murine leukemia L1210 cells were exposed to each aminopolyamine, and the 48-h and 96-h IC50 values were measured (in addition to their effect on polyamine metabolism). In the prokaryotic model, P. aeruginosa was used to study the impact of the synthetic aminopolyamines on its growth and polyamine metabolism. Studies in L1210 cells revealed that 2-aminoputrescine (2-NH2-PUT), and 6-aminospermine (6-NH2-SPM) had no significant impact on cellular growth with 48-h IC50 values >100 μM; while 7-aminospermidine (7-NH2-SPD) had a very moderate effect with a 48-h IC50 of 60 μM and a 96-h IC50 of 9 μM. The aminopolyamine N1,N8-diethyl-7-aminospermidine (7-NH2-DESPD) also showed a mild effect on cellular growth with a 48-h IC50 of 100 μM and a 96-h IC50 of 6 μM. At a concentration of 1 μM, 7-NH2-SPD and 7-NH2-DESPD had a slight impact on ODC by reducing the enzymatic activity to 72% and 79% of control, respectively. The aminopolyamine 6-NH2-SPM was more active by reducing ODC activity to 52% of control. In addition, 6-NH 2-SPM reduced AdoMetDC activity to 70% of control. While 7-NH2 -SPD and 6-NH2-SPM did not significantly stimulate spermidine/spermine- N1-acetyltranslerase (SSAT), 7-NH2-DESPD showed a moderate SSAT stimulation by upregulating SSAT to 303% of control. L1210 cells were able to catabolically convert 7-NH2-SPD to 2-NH 2-PUT and biosynthesize 6-NH2-SPM from 7-NH2-SPD. Besides, when exposed to 6-NH2-SPM, these cells converted this aminopolyamine to 7-NH2-SPD, and then to 2-NH2-PUT. When exposed to 7-NH2-DESPD or 6-NH2-DESPM, deethylation of these diethylated aminopolyamines also occurred inside the L1210 cell, possibly via the SSAT/PAO pathway. In P. aeruginosa, 2-OH-PUT and 7-OH-SPD are not produced endogenously. However, when exposed to 2-OH-PUT, the bacteria elaborated 2-OH-PUT into 7-OH-SPD. A similar scenario occurred in which 2-NH2-PUT was converted to 7-NH2-SPD by P. aeruginosa. This bacterium was incapable of producing 6-NH2-SPM from 7-NH2 -SPD. However, when exposed to 6-NH2-SPM, it was able to metabolize 6-NH2-SPM to 7-NH2-SPD and 2-NH2-PUT. Our results in this dissertation significantly add to the understanding of how various polyamine analogues are metabolically processed in both eukaryotes and prokaryotes.
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650 4 $a Organic chemistry. $3 523952
653 $a Aminopolyamines
653 $a Leukemia
653 $a Pathogenic bacterium
653 $a Pseudomonas aeruginosa
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710 2 $a University of Florida. $e degree granting institution. $3 3759264
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791 $a Ph.D.
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