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Functional roles of polyamines and their metabolite acrolein in eukaryotic cells

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Abstract

Among low molecular weight substances, polyamines (spermidine, spermine and their precursor putrescine) are present in eukaryotic cells at the mM level together with ATP and glutathione. It is expected therefore that polyamines play important roles in cell proliferation and viability. Polyamines mainly exist as a polyamine-RNA complex and regulate protein synthesis. It was found that polyamines enhance translation from inefficient mRNAs. The detailed mechanisms of polyamine stimulation of specific kinds of protein syntheses and the physiological functions of these proteins are described in this review. Spermine is metabolized into acrolein (CH2 = CH–CHO) and hydrogen peroxide (H2O2) by spermine oxidase. Although it is thought that cell damage is mainly caused by reactive oxygen species (O2, H2O2, and •OH), it was found that acrolein is much more toxic than H2O2. Accordingly, the level of acrolein produced becomes a useful biomarker for several tissue-damage diseases like brain stroke. Thus, the mechanisms of cell toxicity caused by acrolein are described in this review.

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Abbreviations

AD:

Alzheimer’s disease

Bmal1:

Brain/muscle Arnt-like 1 protein

CA:

Carotid atherosclerosis

Cct2:

T-complex protein, β-subunit

Chsy1:

Chondroitin synthase 1

CR:

Complementary sequence to the 3’-end of 18S rRNA

Cox4:

One of the subunit of cytochrome C in yeast

CRP:

C-reactive protein

DFMO:

α-Difluoromethylornithine

eEF1A:

Eukaryotic elongation factor 1A

eIF5A:

Eukaryotic initiation factor 5A

EGFP:

Enhanced green fluorescent protein

Ext2:

One of the glycosyltransferases

FDP-Lys:

Nε-(3-Formyl-3,4-dehydropiperidino)-lysine

Gcn5:

One of the histone acetyltransferases

Hat1:

One of the histone acetyltransferases

MCI:

Mild cognitive impairment

MMP:

Matrix metalloproteinase

NAC:

N-Acetylcysteine

PIT:

Photochemically induced thrombosis

pSS:

Primary Sjögren’s syndrome

Rev-Erbα:

A transcriptional repressor of circadian clock gene Bmal1

ROS:

Reactive oxygen species

RRV:

Relative risk value

SBI:

Silent (small) brain infarction

5’-UTR:

5’-Untranslated region

WMH:

White matter hyperintensity

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Acknowledgements

We thank Dr. A. J. Michael for his help in preparing the manuscript. This work was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan (21K06714).

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Igarashi, K., Kashiwagi, K. Functional roles of polyamines and their metabolite acrolein in eukaryotic cells. Amino Acids 53, 1473–1492 (2021). https://doi.org/10.1007/s00726-021-03073-w

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