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Tytuł:
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Melatonin alleviates arginine vasopressin-induced cardiomyocyte apoptosis via increasing Mst1-Nrf2 pathway activity to reduce oxidative stress.
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Autorzy:
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Chen S; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, China.
Li Y; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Fu S; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Li Y; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Wang C; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Sun P; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Li H; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Tian J; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China. Electronic address: .
Du GQ; Department of Ultrasound, The Second Affiliated Hospital of Harbin Medical University, Harbin, China; Department of Ultrasound, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. Electronic address: .
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Źródło:
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Biochemical pharmacology [Biochem Pharmacol] 2022 Dec; Vol. 206, pp. 115265. Date of Electronic Publication: 2022 Sep 29.
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Typ publikacji:
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Journal Article; Research Support, Non-U.S. Gov't
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Język:
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English
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Imprint Name(s):
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Publication: Oxford : Elsevier Science
Original Publication: Oxford, New York [etc.] Paragamon Press.
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MeSH Terms:
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Melatonin*/pharmacology
Myocytes, Cardiac*/drug effects
Myocytes, Cardiac*/pathology
NF-E2-Related Factor 2*/genetics
NF-E2-Related Factor 2*/metabolism
Humans ; Apoptosis ; Arginine Vasopressin/adverse effects ; Cardiomegaly/metabolism ; Oxidative Stress ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Reactive Oxygen Species/metabolism
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Contributed Indexing:
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Keywords: Apoptosis; H9c2 cardiomyoblast; Melatonin; Mst1; Nrf2; Oxidative stress
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Substance Nomenclature:
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113-79-1 (Arginine Vasopressin)
JL5DK93RCL (Melatonin)
0 (NF-E2-Related Factor 2)
0 (Proto-Oncogene Proteins c-bcl-2)
0 (Reactive Oxygen Species)
0 (macrophage stimulating protein)
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Entry Date(s):
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Date Created: 20221002 Date Completed: 20221209 Latest Revision: 20221209
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Update Code:
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20240105
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DOI:
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10.1016/j.bcp.2022.115265
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PMID:
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36183803
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Heart failure patients have elevated arginine vasopressin (AVP) levels, which are involved in inducing peripheral vasoconstriction and cardiac hypertrophy. This hypertrophy, along with cardiomyocyte apoptosis, results from oxidative stress. Therefore, the antioxidant drug, melatonin (Mel), is commonly used to treat cardiac hypertrophy and apoptosis; however, whether it could alleviate AVP-induced myocardialinjury remains to be addressed. In this study, high AVP doses were found to induce H9c2 cardiomyoblast apoptosis, demonstrated by increased terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive cells, pro-apoptotic B-cell lymphoma-2 (Bcl-2)-associated X protein (Bax) up-regulation, and anti-apoptotic Bcl-2 downregulation. This AVP-induced apoptotic increase, along with lowered cell viability, was also associated with higher reactive oxygen species (ROS) levels and lowered mitochondrial membrane potentials (MMP), which were all reversed upon Mel administration. Further investigations found that apoptosis, ROS, and MMP outcomes under high AVP were associated with Mst1-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway suppression, yielding mitochondrial dysfunction, and Mel reversed them via promoting Mst1 phosphorylation, which then activated Nrf2 to increase anti-oxidative enzyme production. These findings were supported by siRNA gene suppression, where knocking down either Nrf2 or Mst1 abrogated the anti-apoptotic effects of Mel in cardiomyoblasts. Therefore, Mel could reduce cardiomyoblast apoptosis under high AVP levels, via Mst1-Nrf2 pathway re-activation, to enhance anti-oxidative responses.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2022 Elsevier Inc. All rights reserved.)
