Einzeltreffer — DigiBib

Abstract: Chronic alcohol intake contributes to high mortality rates due to ethanol-induced cardiac hypertrophy and contractile dysfunction, which are accompanied by increased oxidative stress and disrupted mitophagy. Alpha-lipoic acid (α-LA), a well-known antioxidant, has been shown to protect against cardiac hypertrophy and inflammation. However, little is known about its role and mechanism in the treatment of alcoholic cardiomyopathy. Here, we evaluated the role of α-LA in alcohol-induced cardiac damage by feeding mice a 4.8% (v/v) alcohol diet with or without α-LA for 6 w. Our results suggested that chronic alcohol consumption increased mortality, blood alcohol concentrations, and serum aldehyde levels, but a-LA attenuated the elevations in mortality and aldehydes. Chronic alcohol intake also induced cardiac dysfunction, including enlarged left ventricles, reduced left ventricular ejection fraction, enhanced cardiomyocyte size, and increased serum levels of brain natriuretic peptide, lactate dehydrogenase, and creatine kinase myocardial isoenzyme. Moreover, alcohol intake led to the accumulation of collagen fiber and mitochondrial dysfunction, the effects of which were alleviated by α-LA. In addition, α-LA intake also prevented the increase in reactive oxygen species production and the decrease in mitochondrial number that were observed after alcohol consumption. Chronic alcohol exposure activated PINK1/Parkin-mediated mitophagy. These effects were diminished by α-LA intake by the activation of aldehyde dehydrogenase 2. Our data indicated that α-LA helps protect cardiac cells against the effects of chronic alcohol intake, likely by inhibiting PINK1/Parkin-related mitophagy through the activation of aldehyde dehydrogenase 2.

Competing Interests: The authors report no conflicts of interest.

Titel:	Alpha-lipoic Acid Protects Against Chronic Alcohol Consumption-induced Cardiac Damage by the Aldehyde Dehydrogenase 2-associated PINK/Parkin Pathway.
Autor/in / Beteiligte Person:	Shen, C ; Chen, X ; Cao, Y ; Du, Y ; Xu, X ; Wu, Q ; Lin, L ; Qin, Y ; Meng, R ; Gan, L ; Zhang, J
Zeitschrift:	Journal of cardiovascular pharmacology, Jg. 82 (2023-11-01), Heft 5, S. 407
Veröffentlichung:	Hagerstown, MD : Lippincott Williams & Wilkins ; <i>Original Publication</i>: New York, Raven Press., 2023
Medientyp:	academicJournal
ISSN:	1533-4023 (electronic)
DOI:	10.1097/FJC.0000000000001480
Schlagwort:	Mice Animals Aldehyde Dehydrogenase, Mitochondrial metabolism Stroke Volume Ventricular Function, Left Myocytes, Cardiac Ethanol toxicity Alcohol Drinking adverse effects Alcohol Drinking metabolism Aldehydes metabolism Aldehydes pharmacology Protein Kinases metabolism Cardiomegaly metabolism Aldehyde Dehydrogenase metabolism Aldehyde Dehydrogenase pharmacology Thioctic Acid pharmacology Alcoholism metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [J Cardiovasc Pharmacol] 2023 Nov 01; Vol. 82 (5), pp. 407-418. <i>Date of Electronic Publication: </i>2023 Nov 01. MeSH Terms: Thioctic Acid* / pharmacology ; Alcoholism* / metabolism ; Mice ; Animals ; Aldehyde Dehydrogenase, Mitochondrial / metabolism ; Stroke Volume ; Ventricular Function, Left ; Myocytes, Cardiac ; Ethanol / toxicity ; Alcohol Drinking / adverse effects ; Alcohol Drinking / metabolism ; Aldehydes / metabolism ; Aldehydes / pharmacology ; Protein Kinases / metabolism ; Cardiomegaly / metabolism ; Aldehyde Dehydrogenase / metabolism ; Aldehyde Dehydrogenase / pharmacology References: Andersson C, Schou M, Gustafsson F, et al. Alcohol intake in patients with cardiomyopathy and heart failure: consensus and controversy. Circ Heart Fail. 2022;15:e009459. ; Yu LM, Dong X, Li N, et al. Polydatin attenuates chronic alcohol consumption-induced cardiomyopathy through a SIRT6-dependent mechanism. Food Funct. 2022;13:7302–7319. ; Fernández-Solà J. The effects of ethanol on the heart: alcoholic cardiomyopathy. Nutrients. 2020;12:572. ; Steiner JL, Lang CH. Etiology of alcoholic cardiomyopathy: mitochondria, oxidative stress and apoptosis. Int J Biochem Cell Biol. 2017;89:125–135. ; Wang S, Ren J. Role of autophagy and regulatory mechanisms in alcoholic cardiomyopathy. Biochim Biophys Acta Mol Basis Dis. 2018;1864:2003–2009. ; Nah J, Zablocki D, Sadoshima J. The role of autophagic cell death in cardiac disease. J Mol Cell Cardiol. 2022;173:16–24. ; Dewanjee S, Vallamkondu J, Kalra RS, et al. Autophagy in the diabetic heart: a potential pharmacotherapeutic target in diabetic cardiomyopathy. Ageing Res Rev. 2021;68:101338. ; Wang Y, Jasper H, Toan S, et al. Mitophagy coordinates the mitochondrial unfolded protein response to attenuate inflammation-mediated myocardial injury. Redox Biol. 2021;45:102049. ; Bravo-San Pedro JM, Kroemer G, Galluzzi L. Autophagy and mitophagy in cardiovascular disease. Circ Res. 2017;120:1812–1824. ; Ji H, Wu D, Kimberlee O, et al. Molecular perspectives of mitophagy in myocardial stress: pathophysiology and therapeutic targets. Front Physiol. 2021;12:700585. ; Yang M, Wang S, Fu S, et al. Deletion of the E3 ubiquitin ligase, Parkin, exacerbates chronic alcohol intake-induced cardiomyopathy through an Ambra1-dependent mechanism. Br J Pharmacol. 2021;178:964–982. ; Yan T, Zhao Y, Jiang Z, et al. Acetaldehyde induces cytotoxicity via triggering mitochondrial dysfunction and overactive mitophagy. Mol Neurobiol. 2022;59:3933–3946. ; Zhou H, Zhu P, Wang J, et al. DNA-PKcs promotes alcohol-related liver disease by activating Drp1-related mitochondrial fission and repressing FUNDC1-required mitophagy. Signal Transduct Target Ther. 2019;4:56. ; Xia D, Zhai X, Wang H, et al. Alpha lipoic acid inhibits oxidative stress‐induced apoptosis by modulating of Nrf2 signalling pathway after traumatic brain injury. J Cell Mol Med. 2019;23:4088–4096. ; Hiller S, DeKroon R, Hamlett ED, et al. Alpha-lipoic acid supplementation protects enzymes from damage by nitrosative and oxidative stress. Biochim Biophys Acta. 2016;1860:36–45. ; Lee KJ, Ko YJ, Kang SK, et al. Additive anti-inflammation by a combination of conjugated linoleic acid and α-lipoic acid through molecular interaction between both compounds. Food Sci Biotechnol. 2019;29:419–429. ; Ding Y, Zhang Y, Zhang W, et al. Effects of lipoic acid on ischemia‒reperfusion injury. Oxid Med Cell Longev. 2021;2021:1–15. ; Dugbartey GJ, Wonje QL, Alornyo KK, et al. Alpha-lipoic acid treatment improves adverse cardiac remodelling in the diabetic heart -the role of cardiac hydrogen sulfide-synthesizing enzymes. Biochem Pharmacol. 2022;203:115179. ; Wenzel P, Hink U, Oelze M, et al. Role of reduced lipoic acid in the redox regulation of mitochondrial aldehyde dehydrogenase (ALDH-2) activity: implications for mitochondrial oxidative stress and nitrate tolerance. J Biol Chem. 2007;282:792–799. ; Li W, Yin L, Sun X, et al. Alpha-lipoic acid protects against pressure overload-induced heart failure via ALDH2-dependent Nrf1-FUNDC1 signaling. Cell Death Dis. 2020;11:599. ; Tang X, Chen XF, Wang NY, et al. SIRT2 acts as a cardioprotective deacetylase in pathological cardiac hypertrophy. Circulation. 2017;136:2051–2067. ; Liu J, Killilea DW, Ames BN. Age-associated mitochondrial oxidative decay: improvement of carnitine acetyltransferase substrate-binding affinity and activity in brain by feeding old rats acetyl-L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99:1876–1881. ; Gong Y, Li G, Tao J, et al. Double knockout of Akt2 and AMPK accentuates high fat diet-induced cardiac anomalies through a cGAS-STING-mediated mechanism. Biochim Biophys Acta Mol Basis Dis. 2020;1866:165855. ; Ji W, Wan T, Zhang F, et al. Aldehyde dehydrogenase 2 protects against lipopolysaccharide-induced myocardial injury by suppressing mitophagy. Front Pharmacol. 2021;12:641058. ; Ji W, Wei S, Hao P, et al. Aldehyde dehydrogenase 2 has cardioprotective effects on myocardial ischaemia/reperfusion injury via suppressing mitophagy. Front Pharmacol. 2016;7:101. ; Zhou C, Huang J, Li Q, et al. CYP2J2-derived EETs attenuated ethanol-induced myocardial dysfunction through inducing autophagy and reducing apoptosis. Free Radic Biol Med. 2018;117:168–179. ; Wang C, Li S, Liu Q, et al. Ectopic accumulation of ceramide in cardiomyocytes modulates alcoholic cardiomyopathy via the TLR4-dependent pathway. Alcohol Clin Exp Res. 2022;46:1011–1022. ; Yan T, Zhao Y. Acetaldehyde induces phosphorylation of dynamin-related protein 1 and mitochondrial dysfunction via elevating intracellular ROS and Ca 2+ levels. Redox Biol. 2020;28:101381. ; Zhu Z, Huang Y, Lv L, et al. Acute ethanol exposure-induced autophagy-mediated cardiac injury via activation of the ROS-JNK-Bcl-2 pathway. J Cell Physiol. 2018;233:924–935. ; Matyas C, Varga ZV, Mukhopadhyay P, et al. Chronic plus binge ethanol feeding induces myocardial oxidative stress, mitochondrial and cardiovascular dysfunction, and steatosis. Am J Physiol-Heart Circ Physiol. 2016;310:H1658–H1670. ; Piano MR. Alcohol's effects on the cardiovascular system. Alcohol Res. 2017;38:219–241. ; Tao Y, Zhou H, Huang L, et al. Schisandrin B protects against acute ethanol-induced cardiac injury by downregulating autophagy via the NOX4/ROS pathway. Pharmacology. 2021;106:177–188. ; Laker RC, Drake JC, Wilson RJ, et al. AMPK phosphorylation of ULK1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy. Nat Commun. 2017;8:548. ; Wang W, Liu T, Liu Y, et al. Astaxanthin attenuates alcoholic cardiomyopathy via inhibition of endoplasmic reticulum stress-mediated cardiac apoptosis. Toxicol Appl Pharmacol. 2021;412:115378. ; Steiner JL, Lang CH. Alcoholic cardiomyopathy: disrupted protein balance and impaired cardiomyocyte contractility. Alcohol Clin Exp Res. 2017;41:1392–1401. ; Xu J, Wang L, Zhang L, et al. Mono-2-ethylhexyl phthalate drives progression of PINK1-Parkin-mediated mitophagy via increasing mitochondrial ROS to exacerbate cytotoxicity. Redox Biol. 2021;38:101776. ; Knuppertz L, Warnsmann V, Hamann A, et al. Stress-dependent opposing roles for mitophagy in aging of the ascomycete podospora anserina. Autophagy. 2017;13:1037–1052. ; Yin J, Guo J, Zhang Q, et al. Doxorubicin-induced mitophagy and mitochondrial damage is associated with dysregulation of the PINK1/Parkin pathway. Toxicol Vitro. 2018;51:1–10. ; Samuvel DJ, Li L, Krishnasamy Y, et al. Mitochondrial depolarization after acute ethanol treatment drives mitophagy in living mice. Autophagy. 2022;18:2671–2685. ; Liu Y, You F, Song G, et al. Deficiency in beclin1 attenuates alcohol-induced cardiac dysfunction via inhibition of ferroptosis. Biochim Biophys Acta. 2022;1866:130245. ; Liang B, Xiao T, Long J, et al. Hydrogen sulfide alleviates myocardial fibrosis in mice with alcoholic cardiomyopathy by downregulating autophagy. Int J Mol Med. 2017;40:1781–1791. ; Tian G, Li J, Zhou L. Ginsenoside Rg1 regulates autophagy and endoplasmic reticulum stress via the AMPK/mTOR and PERK/ATF4/CHOP pathways to alleviate alcohol-induced myocardial injury. Int J Mol Med. 2023;52:56. ; Xu Y, Tang Y, Lu J, et al. PINK1-mediated mitophagy protects against hepatic ischemia/reperfusion injury by restraining NLRP3 inflammasome activation. Free Radic Biol Med. 2020;160:871–886. ; Zuo Z, Jing K, Wu H, et al. Mechanisms and functions of mitophagy and potential roles in renal disease. Front Physiol. 2020;11:935. ; Chen CH, Ferreira JCB, Mochly-Rosen D. ALDH2 and cardiovascular disease. Adv Exp Med Biol. 2019;1193:53–67. ; Papatheodorou I, Galatou E, Panagiotidis GD, et al. Cardioprotective effects of PPARβ/δ activation against ischemia/reperfusion injury in rat heart are associated with ALDH2 upregulation, amelioration of oxidative stress and preservation of mitochondrial energy production. Int J Mol Sci. 2021;22:6399. Grant Information: ZR202112020064 Surface Project of National Natural Science Foundation of Shandong; 2020JKNS006 Jining Key Research and Development Project; 82000269 Youth Project of National Natural Science Foundation of China Substance Nomenclature: 73Y7P0K73Y (Thioctic Acid) ; EC 1.2.1.3 (Aldehyde Dehydrogenase, Mitochondrial) ; 3K9958V90M (Ethanol) ; 0 (Aldehydes) ; EC 2.7.- (Protein Kinases) ; EC 1.2.1.3 (Aldehyde Dehydrogenase) Entry Date(s): Date Created: 20230901 Date Completed: 20231109 Latest Revision: 20240418 Update Code: 20240418

Klicken Sie ein Format an und speichern Sie dann die Daten oder geben Sie eine Empfänger-Adresse ein und lassen Sie sich per Email zusenden.

BibTeX Citavi, JabRef, u.a.
(Literaturverwaltung)

PDF kein Volltext!
(Merkzettel, Notizen)

RIS Endnote, Citavi u.a.
(Literaturverwaltung)

MODS
(XML zur Weiterverarbeitung)

oder

Wählen Sie das für Sie passende Zitationsformat und kopieren Sie es dann in die Zwischenablage, lassen es sich per Mail zusenden oder speichern es als PDF-Datei.

Gewünschter Zitations-Stil:

oder

Bitte prüfen Sie, ob die Zitation formal korrekt ist, bevor Sie sie in einer Arbeit verwenden. Benutzen Sie gegebenenfalls den "Exportieren"-Dialog, wenn Sie ein Literaturverwaltungsprogramm verwenden und die Zitat-Angaben selbst formatieren wollen.

Alpha-lipoic Acid Protects Against Chronic Alcohol Consumption-induced Cardiac Damage by the Aldehyde Dehydrogenase 2-associated PINK/Parkin Pathway.