Spermidine

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Spermidine

Description

Spermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.


Reference: Madeo 2018 Science

Spermidine and mitObesity

Work in progress by Gnaiger E 2020-02-18 linked to a preprint in preparation on BME and mitObesity.

References: Spermidine

 YearReferenceOrganismTissue;cell
Tyrrell 2019 Circ Res2019Tyrrell DJ, Blin M, Song J, Wood S, Zhang M, Beard DA, Goldstein D (2019) Age-associated mitochondrial dysfunction accelerates atherogenesis. Circ Res 126:298–314.MouseEndothelial;epithelial;mesothelial cell
Gabandé-Rodríguez 2019 Cells2019Gabandé-Rodríguez E, M Gómez de Las Heras M, Mittelbrunn M (2019) Control of inflammation by calorie restriction mimetics: on the crossroad of autophagy and mitochondria. Cells 2019;9:E82.
Madeo 2018 Science2018Madeo F, Eisenberg T, Pietrocola F, Kroemer G (2018) Spermidine in health and disease. Science 359:eaan2788.Human
Fan 2017 Oncotarget2017Fan J, Yang X, Li J, Shu Z, Dai J, Liu X, Li B, Jia S, Kou X, Yang Y, Chen N (2017) Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget 8:17475–90.RatSkeletal muscle
Eisenberg 2016 Nat Med2016Eisenberg T, Abdellatif M, Schroeder S, Primessnig U, Stekovic S, Pendl T, Harger A, Schipke J, Zimmermann A, Schmidt A, Tong M, Ruckenstuhl C, Dammbrueck C, Gross AS, Herbst V, Magnes C, Trausinger G, Narath S, Meinitzer A, Hu Z, Kirsch A, Eller K, Carmona-Gutierrez D, Büttner S, Pietrocola F, Knittelfelder O, Schrepfer E, Rockenfeller P, Simonini C, Rahn A, Horsch M, Moreth K, Beckers J, Fuchs H, Gailus-Durner V, Neff F, Janik D, Rathkolb B, Rozman J, de Angelis MH, Moustafa T, Haemmerle G, Mayr M, Willeit P, von Frieling-Salewsky M, Pieske B, Scorrano L, Pieber T, Pechlaner R, Willeit J, Sigrist SJ, Linke WA, Mühlfeld C, Sadoshima J, Dengjel J, Kiechl S, Kroemer G, Sedej S, Madeo F (2016) Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med 22:1428-38.MouseHeart
Bonhoure 2015 Genes Dev2015Bonhoure N, Byrnes A, Moir RD, Hodroj W, Preitner F, Praz V, Marcelin G, Chua SC Jr, Martinez-Lopez N, Singh R, Moullan N, Auwerx J, Willemin G, Shah H, Hartil K, Vaitheesvaran B, Kurland I, Hernandez N, Willis IM1 (2015) Loss of the RNA polymerase III repressor MAF1 confers obesity resistance. Genes Dev 29:934-47.MouseLiver
Angiulli 2015 Biochim Biophys Acta2015Angiulli G, Lantella A, Forte E, Angelucci F, Colotti G, Ilari A, Malatesta F (2015) Leishmania infantum trypanothione reductase is a promiscuous enzyme carrying an NADPH:O2 oxidoreductase activity shared by glutathione reductase. Biochim Biophys Acta 1850:1891-7.
Morselli 2011 J Cell Biol2011Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G (2011) Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome. J Cell Biol 192:615–29.Human
Caenorhabditis elegans
Saccharomyces cerevisiae
Rustenbeck 1998 Biochem Pharmacol1998Rustenbeck I, Eggers G, Reiter H, Münster W, Lenzen S (2020) Polyamine modulation of mitochondrial calcium transport. I. Stimulatory and inhibitory effects of aliphatic polyamines, aminoglucosides and other polyamine analogues on mitochondrial calcium uptake. Biochem Pharmacol 56:977–85.RatLiver


MitoPedia: mitObesity drugs

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TermAbbreviationDescription
CurcuminCurcumin has been shown to possess significant anti-inflammatory, anti-oxidant, anti-carcinogenic, anti-mutagenic, anti-coagulant and anti-infective effects. The protective effects of curcumin on rat heart mitochondrial injuries induced by in vitro anoxia–reoxygenation were evaluated by Xu et al 2013. It was found that curcumin added before anoxia or immediately prior to reoxygenation exhibited remarkable protective effects against anoxia–reoxygenation induced oxidative damage to mitochondria.
ElamipretideBendaviaBendavia (Elamipretide) was developed as a mitochondria-targeted drug against degenerative diseases, including cardiac ischemia-reperfusion injury. Clinical trials showed variable results. It is a cationic tetrapeptide which readily passes cell membranes, associates with cardiolipin in the mitochondrial inner membrane. Supercomplex-associated CIV activity significantly improved in response to elamipretide treatment in the failing human heart.
FlavonoidsFlavonoids are a group of bioactive polyphenols with potential antioxidant and anti-inflammatory effects, abundant in fruits and vegetables, and in some medicinal herbs. Flavonoids are synthesized in plants from phenylalanine. Dietary intake of flavonoids as nutraceuticals is discussed for targeting T2D and other degenerative diseases.
MelatoninaMTMelatonin (N-acetyl-5-methoxytryptamine, aMT) is a highly conserved molecule present in unicellular to vertebrate organisms. Melatonin is synthesized from tryptophan in the pinealocytes by the pineal gland and also is produced in other organs, tissues and fluids (extrapineal melatonin). Melatonin has lipophilic and hydrophilic nature which allows it to cross biological membranes. Therefore, melatonin is present in all subcellular compartments predominantly in the nucleus and mitochondria. Melatonin has pleiotropic functions with powerful antioxidant, anti-inflammatory and oncostatic effects with a wide spectrum of action particularly at the level of mitochondria. » MiPNet article
MetforminMetformin is mainly known as an important antidiabetic drug which is effective, however, in a wide spectrum of degenerative diseases. It is an inhibitor of Complex I.
RapamycinRapamycin is an inhibitor of the mammalian/mechanistic target of rapamycin, complex 1 (mTORC1). Rapamycin induces autophagy and dyscouples mitochondrial respiration. Rapamycin delays senescence in human cells, and extends lifespan in mice without detrimental effects on mitochondrial fitness in skeletal muscle.
ResveratrolResveratrol is a natural bioactive phenol prouced by several plants with antioxidant and anti-inflammatory effects. Dietary intake as nutraceutical is discussed for targeting mitochondria with a wide spectrum of action in degenerative diseases.
SpermidineSpermidine is a polycationic bioactive polyamine mainly found in wheat germ, soybean and various vegetables, involved in the regulation of mitophagy, cell growth and cell death. Like other caloric restriction mimetics, spermidine is effective in cardioprotection, neuroprotection and anticancer immunosuppression by preserving mitochondrial function and control of autophagy.
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