Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography

Hyvönen, Tapani; Keinänen, Tuomo A.; Khomutov, Alex R.; Khomutov, R. M.; Eloranta, Terho O.

doi:10.1016/0378-4347(92)80093-6

Cited by 120 publications

(81 citation statements)

References 12 publications

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“…Polyamines and their acetylated derivatives were determined using HPLC as described by Hyvönen et al (1992). Ethylated analogs were measured as described by Kabra et al (1986).…”

Section: Ssat Activity and Polyamine Concentrationsmentioning

confidence: 99%

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase

Hyvönen

Uimari²,

Keinänen³

et al. 2006

RNA

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Spermidine/spermine N 1 -acetyltransferase (SSAT), the rate-controlling enzyme in the interconversion of spermidine and spermine, is regulated by polyamines and their analogs at many levels of gene expression. Recently, SSAT pre-mRNA has been shown to undergo alternative splicing by inclusion of an exon that contains premature termination codons. In the present study, we show that alterations in the intracellular polyamine level resulted in a change in the relative abundance of SSAT transcripts. Addition of polyamines or their N-diethylated analogs reduced the amount of the variant transcript, whereas polyamine depletion by 2-difluoromethylornithine or MG-132 enhanced the exon inclusion. Experiments performed with protein synthesis inhibitors and siRNA-mediated down-regulation of Upf1 protein verified that the variant transcript was degraded by nonsensemediated mRNA decay (NMD). Interestingly, several proteins have been shown to regulate their expression by alternative splicing-coupled NMD, termed regulated unproductive splicing and translation (RUST). Our present results suggest that in the case of SSAT, RUST is mediated by polyamines, and this system functions to fine-tune the polyamine metabolism.

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“…Polyamines and their acetylated derivatives were determined using HPLC as described by Hyvönen et al (1992). Ethylated analogs were measured as described by Kabra et al (1986).…”

Section: Ssat Activity and Polyamine Concentrationsmentioning

confidence: 99%

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase

Hyvönen

Uimari²,

Keinänen³

et al. 2006

RNA

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“…The homogenates were diluted 1:9 in 5% SSA solution containing 10 M 1,7-diaminoheptane, kept on ice for 20 min, and centrifuged at 14,000g for 30 min. Polyamines, TETA, and its acetylated derivates were analyzed by HPLC following the previously published method by Hyvönen et al (1992). In the biological sample matrix stability test, aliquots of 200 l of supernatant fractions were neutralized using 14 l of Na 2 CO 3 (2 M) to prevent intramolecular N-acetyl migration of N 1 AcTETA.…”

Section: Methodsmentioning

confidence: 99%

Complex N-Acetylation of Triethylenetetramine

Cerrada-Gimenez¹,

Weisell²,

Hyvönen³

et al. 2011

Drug Metab Dispos

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“…Polyamines from 3-month-old female SSAT and Wt mice were determined by using high-performance liquid chromatography (20). SSAT activity was assayed as described previously (3).…”

Section: Animalsmentioning

confidence: 99%

Enhanced Polyamine Catabolism Alters Homeostatic Control of White Adipose Tissue Mass, Energy Expenditure, and Glucose Metabolism

Pirinen

Kuulasmaa

Pietilä

et al. 2007

Molecular and Cellular Biology

118

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Peroxisome proliferator-activated receptor ␥ coactivator 1␣ (PGC-1␣) is an attractive candidate gene for type 2 diabetes, as genes of the oxidative phosphorylation (OXPHOS) pathway are coordinatively downregulated by reduced expression of PGC-1␣ in skeletal muscle and adipose tissue of patients with type 2 diabetes. Here we demonstrate that transgenic mice with activated polyamine catabolism due to overexpression of spermidine/spermine N 1 -acetyltransferase (SSAT) had reduced white adipose tissue (WAT) mass, high basal metabolic rate, improved glucose tolerance, high insulin sensitivity, and enhanced expression of the OXPHOS genes, coordinated by increased levels of PGC-1␣ and 5-AMP-activated protein kinase (AMPK) in WAT. As accelerated polyamine flux caused by SSAT overexpression depleted the ATP pool in adipocytes of SSAT mice and N 1 ,N 11 -diethylnorspermine-treated wild-type fetal fibroblasts, we propose that low ATP levels lead to the induction of AMPK, which in turn activates PGC-1␣ in WAT of SSAT mice. Our hypothesis is supported by the finding that the phenotype of SSAT mice was reversed when the accelerated polyamine flux was reduced by the inhibition of polyamine biosynthesis in WAT. The involvement of polyamine catabolism in the regulation of energy and glucose metabolism may offer a novel target for drug development for obesity and type 2 diabetes.Type 2 diabetes is a growing epidemic worldwide. Defects in insulin secretion and insulin action are fundamental disorders of this disease (30). Several mechanisms regulating insulin secretion and insulin action have been identified, but none of them is likely to explain completely the risk of type 2 diabetes. Previous studies have revealed novel mechanisms, distinct from the insulin signaling pathway, for type 2 diabetes. Mootha et al. (36) identified a set of genes involved in oxidative phosphorylation (OXPHOS), the expression of which was coordinately decreased in human diabetic muscle. Similarly, Patti et al. (40) found the downregulation of OXPHOS not only in individuals with type 2 diabetes but also in their first-degree relatives. In both of these studies, decreased peroxisome proliferator-activated receptor (PPAR) ␥ coactivator 1␣ (PGC-1␣) expression was responsible for the downregulation of OX PHOS genes. In addition, the expression of PGC-1␣ has been shown to be downregulated in white adipose tissue (WAT) of insulin-resistant (15) and morbidly obese (50) subjects.PGC-1␣ was first identified as a coactivator of PPAR␥ (45), and it plays a critical role in the regulation of adaptive thermogenesis. Subsequent studies have demonstrated that PGC-1␣ regulates mitochondrial biogenesis (49), uncoupling (45, 56), fatty acid oxidation (61), OXPHOS (36), glucose transport in muscle (35), hepatic gluconeogenesis (64), and skeletal muscle fiber-type switching (44). PGC-1␣ is highly expressed in brown adipose tissue (BAT), heart, and skeletal muscle and moderately expressed in liver, but a low expression level is found in WAT. The expression of PGC-1␣ is ind...

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Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography

Cited by 120 publications

References 12 publications

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase

Complex N-Acetylation of Triethylenetetramine

Enhanced Polyamine Catabolism Alters Homeostatic Control of White Adipose Tissue Mass, Energy Expenditure, and Glucose Metabolism

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Monitoring of the uptake and metabolism of aminooxy analogues of polyamines in cultured cells by high-performance liquid chromatography

Cited by 120 publications

References 12 publications

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N1-acetyltransferase

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N1-acetyltransferase

Complex N-Acetylation of Triethylenetetramine

Enhanced Polyamine Catabolism Alters Homeostatic Control of White Adipose Tissue Mass, Energy Expenditure, and Glucose Metabolism

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Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase

Polyamine-regulated unproductive splicing and translation of spermidine/spermine N¹-acetyltransferase