Polyamines: therapeutic perspectives in oxidative stress and inflammatory diseases

Hussain, Tarique; Tan, Bin; Ren, Wenkai; Rahu, Najma; Dad, Rahim; Kalhoro, Dildar Hussain; Yin, Yulong

doi:10.1007/s00726-017-2447-9

Cited by 47 publications

(33 citation statements)

References 97 publications

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“…The first gene SAT1 catalyzes the acetylation of polyamines (spermidine and spermine) and carries it out of the cell. The polyamine excess is a prominent source of oxidative stress that can increase inflammatory response (Hussain et al, 2017). Polyamines have also been connected with the immune system (Pérez-Cano et al, 2003).…”

Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

Alonso

Diambra

2020

Front. Cell Dev. Biol.

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Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.

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Section: Resultsmentioning

confidence: 99%

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

Alonso

Diambra

2020

Front. Cell Dev. Biol.

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“…To our knowledge, this is the first report that directly connects these pathways to mitochondrial function. The roles of polyamines in cell biology are still poorly understood and are linked to effects on cell proliferation, chromatin configuration, gene transcription, and even mitochondrial calcium homeostasis [ 34 , 35 ]. Whether the changes in polyamine levels we identified to be associated with mitochondrial dysfunction are sufficient to affect any of these processes requires further studies.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation

et al. 2018

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Mitochondrial function affects many aspects of cellular physiology, and, most recently, its role in epigenetics has been reported. Mechanistically, how mitochondrial function alters DNA methylation patterns in the nucleus remains ill defined. Using a cell culture model of induced mitochondrial DNA (mtDNA) depletion, in this study we show that progressive mitochondrial dysfunction leads to an early transcriptional and metabolic program centered on the metabolism of various amino acids, including those involved in the methionine cycle. We find that this program also increases DNA methylation, which occurs primarily in the genes that are differentially expressed. Maintenance of mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation in the context of mtDNA loss rescues methionine salvage and polyamine synthesis and prevents changes in DNA methylation and gene expression but does not affect serine/folate metabolism or transsulfuration. This work provides a novel mechanistic link between mitochondrial function and epigenetic regulation of gene expression that involves polyamine and methionine metabolism responding to changes in the tricarboxylic acid (TCA) cycle. Given the implications of these findings, future studies across different physiological contexts and in vivo are warranted.

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“…A review by Hussain et al covered the general molecular mechanisms for spermine and spermidine involvement in OS induction in various pathologies, as well as possible therapies for OS correction involving these polyamines [59]. In the pre-sent review, we attempt to determine the role of polyamines in OS induction in the pathogenesis of PD, taking into account their selectivity in the substantia nigra.…”

Section: The Role Of Polyamines In Os Induction In Pdmentioning

confidence: 99%

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

et al. 2019

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Parkinson's disease (PD) is a systemic neurodegenerative disease characterized by tremor, rigidity, bradykinesia, and stooping posture. When more than 60% of dopaminergic neurons in the substantia nigra of the brain have died, motor symptoms manifest in PD. Currently, oxidative stress (OS) is considered to be one of the leading factors provoking death of dopaminergic neurons in PD. This review is concerned with the role of polyamines in PD, especially focusing on their role in OS induction. Polyamines (putrescine, cadaverine, spermidine and spermine) are involved in many molecular mechanisms, including cell proliferation and differentiation, gene transcription and translation, modulation of the functional activity of ion channels and receptors, and other vital processes. It is worth noting that under physiological conditions polyamines are antioxidants. It has been shown that spermine oxidase (SMOX) is up-regulated in PD, activating polyamine breakdown, which leads to excessive formation of toxic aldehydes (such as acrolein), H 2 O 2 (a strong cytostatic) and ammonia (a toxic substance). Polyamines are also involved in the pathogenetic mechanism of α-synuclein modification resulting in the formation of Lewy bodies. This review provides data on the changes in polyamine levels at later stages of the disease. The review also examines the role of polyamines, as gliotransmitters, in regulating neural function and vice versa. The mechanisms of polyamine "pumping" from neurons to glia can be considered factors of OS regulation in neurons. Prolonged accumulation of polyamines in glia can lead to oxidation of polyamines and therefore potentially to gliosis in PD. The exact mechanisms of this process are, however, not clear. Answering the questions regarding the role of polyamines in gliosis development and pathogenesis of PD is necessary for treating cognitive impairment in patients with PD, which is particularly important.

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Polyamines: therapeutic perspectives in oxidative stress and inflammatory diseases

Cited by 47 publications

References 97 publications

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

SARS-CoV-2 Codon Usage Bias Downregulates Host Expressed Genes With Similar Codon Usage

Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation

Polyamines in Parkinson’s Disease: Their Role in Oxidative Stress Induction and Protein Aggregation

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