scholarly journals Regulating Polyamine Metabolism by miRNAs in Diabetic Cardiomyopathy

2021 ◽  
Vol 21 (12) ◽  
Author(s):  
Tyler N. Kambis ◽  
Hadassha M. N. Tofilau ◽  
Flobater I. Gawargi ◽  
Surabhi Chandra ◽  
Paras K. Mishra
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Ketone Bodies ◽  
Cardiac Metabolism ◽  
Translational Repression ◽  
Polyamine Metabolism ◽  
Polyamine Biosynthesis ◽  
Polyamine Synthesis ◽  
Circulating Levels ◽  
Insulin Like Activity

Abstract Purpose of Review Insulin is at the heart of diabetes mellitus (DM). DM alters cardiac metabolism causing cardiomyopathy, ultimately leading to heart failure. Polyamines, organic compounds synthesized by cardiomyocytes, have an insulin-like activity and effect on glucose metabolism, making them metabolites of interest in the DM heart. This review sheds light on the disrupted microRNA network in the DM heart in relation to developing novel therapeutics targeting polyamine biosynthesis to prevent/mitigate diabetic cardiomyopathy. Recent Findings Polyamines prevent DM-induced upregulation of glucose and ketone body levels similar to insulin. Polyamines also enhance mitochondrial respiration and thereby regulate all major metabolic pathways. Non-coding microRNAs regulate a majority of the biological pathways in our body by modulating gene expression via mRNA degradation or translational repression. However, the role of miRNA in polyamine biosynthesis in the DM heart remains unclear. Summary This review discusses the regulation of polyamine synthesis and metabolism, and its impact on cardiac metabolism and circulating levels of glucose, insulin, and ketone bodies. We provide insights on potential roles of polyamines in diabetic cardiomyopathy and putative miRNAs that could regulate polyamine biosynthesis in the DM heart. Future studies will unravel the regulatory roles these miRNAs play in polyamine biosynthesis and will open new doors in the prevention/treatment of adverse cardiac remodeling in diabetic cardiomyopathy.

scholarly journals Polyamine Metabolism in Fungi with Emphasis on Phytopathogenic Species

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Laura Valdés-Santiago ◽  
José Antonio Cervantes-Chávez ◽  
Claudia Geraldine León-Ramírez ◽  
José Ruiz-Herrera
Keyword(s):  
Phytopathogenic Fungi ◽  
Polyamine Metabolism ◽  
Polyamine Biosynthesis ◽  
Polyamine Synthesis ◽  
Cell Functions ◽  
Host Fungus ◽  
Development And Differentiation ◽  
The Difference ◽  
Living Organisms

Polyamines are essential metabolites present in all living organisms, and this subject has attracted the attention of researchers worldwide interested in defining their mode of action in the variable cell functions in which they are involved, from growth to development and differentiation. Although the mechanism of polyamine synthesis is almost universal, different biological groups show interesting differences in this aspect that require to be further analyzed. For these studies, fungi represent interesting models because of their characteristics and facility of analysis. During the last decades fungi have contributed to the understanding of polyamine metabolism. The use of specific inhibitors and the isolation of mutants have allowed the manipulation of the pathway providing information on its regulation. During host-fungus interaction polyamine metabolism suffers striking changes in response to infection, which requires examination. Additionally the role of polyamine transporter is getting importance because of its role in polyamine regulation. In this paper we analyze the metabolism of polyamines in fungi, and the difference of this process with other biological groups. Of particular importance is the difference of polyamine biosynthesis between fungi and plants, which makes this process an attractive target for the control of phytopathogenic fungi.

Polyamine metabolism and function

1982 ◽  
Vol 243 (5) ◽  
pp. C212-C221 ◽  
Author(s):  
A. E. Pegg ◽  
P. P. McCann
Keyword(s):  
Molecular Weight ◽  
Tissue Growth ◽  
Polyamine Metabolism ◽  
Organic Cations ◽  
Low Molecular Weight ◽  
Polyamine Biosynthesis ◽  
Polyamine Content ◽  
And Function ◽  
Specific Inhibitors

Polyamines are ubiquitous organic cations of low molecular weight. The content of these amines is closely regulated by the cell according to the state of growth. The reactions responsible for the biosynthesis and interconversion of the polyamines and their precursor putrescine are described and the means by which polyamine content can be varied in response to exogenous stimuli are discussed. The role of polyamines in the cell cycle, cell division, tissue growth, and differentiation is considered. Recent studies using highly specific inhibitors of polyamine biosynthesis such as alpha-difluoromethylornithine to prevent accumulation of polyamines have indicated that the synthesis of polyamines is intimately associated with these processes. Such inhibitors have great potential for investigation of the cellular role of polyamines.

scholarly journals Molecular Mechanisms and Epigenetic Regulation in Diabetic Cardiomyopathy

2021 ◽  
Vol 8 ◽  
Author(s):  
Anupam Mittal ◽  
Rajni Garg ◽  
Ajay Bahl ◽  
Madhu Khullar
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Molecular Mechanisms ◽  
Cardiac Metabolism ◽  
Molecular Pathways ◽  
Myocardial Apoptosis ◽  
Epigenetic Modifiers ◽  
Artery Disease ◽  
And Function ◽  
Lifestyle Disease

Diabetes mellitus (DM) is an important lifestyle disease. Type 2 diabetes is one of the prime contributors to cardiovascular diseases (CVD) and diabetic cardiomyopathy (DbCM) and leads to increased morbidity and mortality in patients with DM. DbCM is a typical cardiac disease, characterized by cardiac remodeling in the presence of DM and in the absence of other comorbidities such as hypertension, valvular diseases, and coronary artery disease. DbCM is associated with defective cardiac metabolism, altered mitochondrial structure and function, and other physiological and pathophysiological signaling mechanisms such as oxidative stress, inflammation, myocardial apoptosis, and autophagy. Epigenetic modifiers are crucial players in the pathogenesis of DbCM. Thus, it is important to explore the role of epigenetic modifiers or modifications in regulating molecular pathways associated with DbCM. In this review, we have discussed the role of various epigenetic mechanisms such as histone modifications (acetylation and methylation), DNA methylation and non-coding RNAs in modulating molecular pathways involved in the pathophysiology of the DbCM.

scholarly journals Protective role of fructose 1,6-bisphosphate during CCl4 hepatotoxicity in rats

1989 ◽  
Vol 262 (3) ◽  
pp. 721-725 ◽  
Author(s):  
S B Rao ◽  
H M Mehendale
Keyword(s):  
Tissue Repair ◽  
Protective Role ◽  
Polyamine Metabolism ◽  
Polyamine Synthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Intermediary Metabolite ◽  
Ccl4 Treatment ◽  
Hepatocellular Regeneration ◽  
Fructose 1,6 Bisphosphate

Rats were injected intraperitoneally with CCl4 (2.5 ml/kg body wt.) and the hepatotoxicity was compared with that of rats receiving the same dose of CCl4 and an intraperitoneal injection of fructose 1,6-bisphosphate (2 g/kg body wt.). A 50-70% decrease in plasma aspartate aminotransferase and alanine aminotransferase activities was observed in the latter treatment, indicating a protective role of the sugar bisphosphate in CCl4 hepatotoxicity. The protection was accompanied by elevated hepatic activities of ornithine decarboxylase at 2, 6 and 24 h, S-adenosylmethionine decarboxylase at 6 h, and spermidine N1-acetyltransferase at 2 h. The increase in the enzymes involved in polyamine metabolism was shown in our previous work [Rao, Young & Mehendale (1989) J. Biochem. Toxicol. 4, 55-63] to correlate with increased polyamine synthesis or interconversion, which was related to the extent of hepatocellular regeneration. The hepatic contents of fructose 1,6-bisphosphate and ATP significantly decreased after CCl4 treatment, and administration of the sugar bisphosphate increased hepatic ATP. Fructose 1,6-bisphosphate, an intermediary metabolite of the glycolytic pathway, may decrease CCl4 toxicity by increasing the ATP in the hepatocytes. The ATP generated is useful for hepatocellular regeneration and tissue repair, events which enable the liver to overcome CCl4 injury.

scholarly journals Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone)

1973 ◽  
Vol 132 (3) ◽  
pp. 537-540 ◽  
Author(s):  
A. E. Pegg
Keyword(s):  
Rat Liver ◽  
Intraperitoneal Injection ◽  
Essential Role ◽  
Complete Inhibition ◽  
Polyamine Metabolism ◽  
Polyamine Synthesis ◽  
Liver And Kidney

The effect of methylglyoxal bis(guanylhydrazone), a substance known to inhibit putrescine-dependent S-adenosyl-l-methionine decarboxylase, on polyamine metabolism in liver and kidney was investigated. Almost complete inhibition of the incorporation of putrescine into spermidine was obtained up to 8h after administration of 80mg of methylglyoxal bis(guanylhydrazone)/kg body wt. by intraperitoneal injection. However, by 20h after administration of the inhibitor spermidine synthesis was resumed. Considerable accumulation of putrescine occurred during this period (up to 3 times control concentrations in both tissues), but there was only a slight fall in the spermidine content. These results suggest that the putrescine-activated S-adenosyl-l-methionine decarboxylase plays an essential role in spermidine biosynthesis in rat liver and kidney, and the possibility of using methylglyoxal bis(guanylhydrazone) to study the role of polyamine synthesis in growth is discussed.

scholarly journals The Emerging Clinical Role of Spermine in Prostate Cancer

2021 ◽  
Vol 22 (9) ◽  
pp. 4382
Author(s):  
Qiang Peng ◽  
Christine Yim-Ping Wong ◽  
Isabella Wai-yin Cheuk ◽  
Jeremy Yuen-Chun Teoh ◽  
Peter Ka-Fung Chiu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Polyamine Metabolism ◽  
Clinical Role ◽  
Polyamine Biosynthesis ◽  
Ongoing Research ◽  
Polyamine Analogues ◽  
Phenotype Transformation ◽  
And Function ◽  
Apoptosis Regulation

Spermine, a member of polyamines, exists in all organisms and is essential for normal cell growth and function. It is highly expressed in the prostate compared with other organs and is detectable in urine, tissue, expressed prostatic secretions, and erythrocyte. A significant reduction of spermine level was observed in prostate cancer (PCa) tissue compared with benign prostate tissue, and the level of urinary spermine was also significantly lower in men with PCa. Decreased spermine level may be used as an indicator of malignant phenotype transformation from normal to malignant tissue in prostate. Studies targeting polyamines and key rate-limiting enzymes associated with spermine metabolism as a tool for PCa therapy and chemoprevention have been conducted with various polyamine biosynthesis inhibitors and polyamine analogues. The mechanism between spermine and PCa development are possibly related to the regulation of polyamine metabolism, cancer-driving pathways, oxidative stress, anticancer immunosurveillance, and apoptosis regulation. Although the specific mechanism of spermine in PCa development is still unclear, ongoing research in spermine metabolism and its association with PCa pathophysiology opens up new opportunities in the diagnostic and therapeutic roles of spermine in PCa management.

scholarly journals Forced expression of antizyme abolishes ornithine decarboxylase activity, suppresses cellular levels of polyamines and inhibits cell growth

1994 ◽  
Vol 304 (1) ◽  
pp. 183-187 ◽  
Author(s):  
Y Murakami ◽  
S Matsufuji ◽  
Y Miyazaki ◽  
S Hayashi
Keyword(s):  
Cell Growth ◽  
Ornithine Decarboxylase ◽  
Polyamine Metabolism ◽  
Decarboxylase Activity ◽  
Inhibitory Protein ◽  
Polyamine Biosynthesis ◽  
Rapid Degradation ◽  
Physiological Importance ◽  
Key Enzyme

Ornithine decarboxylase (ODC) is a key enzyme in polyamine biosynthesis. It is a short-lived protein and negatively regulated by its products, polyamines. Its degradation is accelerated by the binding of antizyme, an ODC-inhibitory protein induced by polyamines. To evaluate the physiological importance of antizyme we examined the effect of forced expression of antizyme on cellular ODC and polyamine levels and cell growth. Antizyme almost completely abolished the induction of ODC by growth stimuli. This may have been caused by antizyme-induced rapid degradation of newly synthesized ODC, since the half-life of ODC complexes with antizyme was less than 5 min. Forced expression of antizyme caused reductions of cellular putrescine and spermidine levels, and inhibited cell growth, which was partially restored by the addition of putrescine. These observations suggested a critically important role of antizyme in polyamine metabolism.

scholarly journals The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Zhila Maghbooli ◽  
Abdorreza Naser Moghadasi ◽  
Nasim Rezaeimanesh ◽  
Abolfazl Omidifar ◽  
Tarlan Varzandi ◽  
...  
Keyword(s):  
Insulin Sensitivity ◽  
Neuromyelitis Optica ◽  
Serum Levels ◽  
Spectrum Disorder ◽  
Control Group ◽  
Neuromyelitis Optica Spectrum Disorder ◽  
Downstream Signaling ◽  
Reduce Insulin Sensitivity ◽  
Circulating Levels

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is associated with inflammatory mediators that may also trigger downstream signaling pathways leading to reduce insulin sensitivity. Methods We aimed to determine the risk association of hyperinsulinemia in NMOSD patients with seropositive AQP4-IgG and the serum levels of interleukin (IL)-6 and IL-17A compared with the control group. Serum levels of metabolic (Insulin, Fasting Blood Sugar (FBS), lipid profile) and inflammatory (IL-6 and IL-17) markers were assessed in 56 NMOSD patients and 100 controls. Results Hyperinsulinemia was more prevalent in NMOSD patients independent of age, sex and body mass index (BMI) (48.2% vs. 26%, p = 0.005) compared to control group. After adjusting age, sex and BMI, there was significant association between lower insulin sensitivity (IS) and NMOSD risk (95% CI: Beta = 0.73, 0.62 to 0.86, p = 0.0001). Circulating levels of IL-6 and IL-17 were higher in NMOSD patients, and only IL-6 had an effect modifier for the association between lower insulin sensitivity and NMOSD risk. Conclusions Our data suggests that inflammatory pathogenesis of NMOSD leads to hyperinsulinemia and increases the risk of insulin resistance.

scholarly journals Overexpression of arginine decarboxylase in transgenic plants

1997 ◽  
Vol 325 (2) ◽  
pp. 331-337 ◽  
Author(s):  
Daniel BURTIN ◽  
Anthony J. MICHAEL
Keyword(s):  
Transgenic Plants ◽  
Arginine Decarboxylase ◽  
Polyamine Metabolism ◽  
Morphological Development ◽  
Polyamine Biosynthesis ◽  
Adenosylmethionine Decarboxylase ◽  
Two Generations ◽  
Key Enzyme ◽  
Polyamine Conjugate ◽  
And Control

The activity of arginine decarboxylase (ADC), a key enzyme in plant polyamine biosynthesis, was manipulated in two generations of transgenic tobacco plants. Second-generation transgenic plants overexpressing an oat ADC cDNA contained high levels of oat ADC transcript relative to tobacco ADC, possessed elevated ADC enzyme activity and accumulated 10–20-fold more agmatine, the direct product of ADC. In the presence of high levels of the precursor agmatine, no increase in the levels of the polyamines putrescine, spermidine and spermine was detected in the transgenic plants. Similarly, the activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase were unchanged. No diversion of polyamine metabolism into the hydroxycinnamic acid–polyamine conjugate pool or into the tobacco alkaloid nicotine was detected. Activity of the catabolic enzyme diamine oxidase was the same in transgenic and control plants. The elevated ADC activity and agmatine production were subjected to a metabolic/physical block preventing increased, i.e. deregulated, polyamine accumulation. Overaccumulation of agmatine in the transgenic plants did not affect morphological development.

scholarly journals Role of CCR2 in the Development of Streptozotocin-Treated Diabetic Cardiomyopathy

Diabetes ◽  
2019 ◽  
Vol 68 (11) ◽  
pp. 2063-2073 ◽  
Author(s):  
Xin Tan ◽  
Lizhi Hu ◽  
Zhiping Shu ◽  
Long Chen ◽  
Xiangrao Li ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy
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