دورية أكاديمية
أعرض في EDS

Attenuating PI3K/Akt- mTOR pathway reduces dihydrosphingosine 1 phosphate mediated collagen synthesis and hypertrophy in primary cardiac cells.

التفاصيل البيبلوغرافية
العنوان: Attenuating PI3K/Akt- mTOR pathway reduces dihydrosphingosine 1 phosphate mediated collagen synthesis and hypertrophy in primary cardiac cells.
المؤلفون: Magaye RR; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia., Savira F; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia., Hua Y; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia; School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China., Xiong X; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia; Shanghai Institute of Heart Failure, Research Centre for Translational Medicine, Shanghai East Hospital, Tongji University, School of Medicine, Shanghai 200120, China., Huang L; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia., Reid C; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia; School of Public Health School, Curtin University, Perth, Australia., Flynn BL; Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia., Kaye D; Heart Failure Research Group, Baker Heart and Diabetes Institute, Melbourne, Australia., Liew D; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia., Wang BH; Biomarker Discovery Laboratory, Baker Heart and Diabetes Institute, Melbourne, Australia; Monash Centre of Cardiovascular Research and Education in Therapeutics, Melbourne, Australia. Electronic address: bing.wang@baker.edu.au.
المصدر: The international journal of biochemistry & cell biology [Int J Biochem Cell Biol] 2021 May; Vol. 134, pp. 105952. Date of Electronic Publication: 2021 Feb 17.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 9508482 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1878-5875 (Electronic) Linking ISSN: 13572725 NLM ISO Abbreviation: Int J Biochem Cell Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Exeter, England ; Tarrytown, NY, U.S.A. : Pergamon, c1995-
مواضيع طبية MeSH: Cardiomegaly/*prevention & control , Collagen/*metabolism , Myocytes, Cardiac/*metabolism , Phosphatidylinositol 3-Kinase/*chemistry , Proto-Oncogene Proteins c-akt/*antagonists & inhibitors , Sphingosine/*analogs & derivatives , TOR Serine-Threonine Kinases/*antagonists & inhibitors, Animals ; Animals, Newborn ; Cardiomegaly/metabolism ; Cardiomegaly/pathology ; Cells, Cultured ; Fibroblasts/metabolism ; Fibroblasts/pathology ; Fibrosis/metabolism ; Fibrosis/pathology ; Fibrosis/prevention & control ; Myocytes, Cardiac/pathology ; Phosphatidylinositol 3-Kinase/metabolism ; Phosphoinositide-3 Kinase Inhibitors/pharmacology ; Rats ; Signal Transduction ; Sphingosine/pharmacology ; Transforming Growth Factor beta/metabolism
مستخلص: Cardiac fibrosis and myocyte hypertrophy play contributory roles in the progression of diseases such as heart Failure (HF) through what is collectively termed cardiac remodelling. The phosphoinositide 3- kinase (PI3K), protein kinase B (Akt) and mammalian target for rapamycin (mTOR) signalling pathway (PI3K/Akt- mTOR) is an important pathway in protein synthesis, cell growth, cell proliferation, and lipid metabolism. The sphingolipid, dihydrosphingosine 1 phosphate (dhS1P) has been shown to bind to high density lipids in plasma. Unlike its analog, spingosine 1 phosphate (S1P), the role of dhS1P in cardiac fibrosis is still being deciphered. This study was conducted to investigate the effect of dhS1P on PI3K/Akt signalling in primary cardiac fibroblasts and myocytes. Our findings demonstrate that inhibiting PI3K reduced collagen synthesis in neonatal cardiac fibroblasts (NCFs), and hypertrophy in neonatal cardiac myocytes (NCMs) induced by dhS1P, in vitro. Reduced activation of the PI3K/Akt- mTOR signalling pathway led to impaired translation of fibrotic proteins such as collagen 1 (Coll1) and transforming growth factor β (TGFβ) and inhibited the transcription and translation of tissue inhibitor of matrix metalloproteinase 1 (TIMP1). PI3K inhibition also affected the gene expression of S1P receptors and enzymes such as the dihydroceramide delta 4 desaturase (DEGS1) and sphingosine kinase 1 (SK1) in the de novo sphingolipid pathway. While in myocytes, PI3K inhibition reduced myocyte hypertrophy induced by dhS1P by reducing skeletal muscle α- actin (αSKA) mRNA expression, and protein translation due to increased glycogen synthase kinase 3β (GSK3β) mRNA expression. Our findings show a relationship between the PI3K/Akt- mTOR signalling cascade and exogenous dhS1P induced collagen synthesis and myocyte hypertrophy in primary neonatal cardiac cells.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
فهرسة مساهمة: Keywords: Cardiac remodelling; Dihydrosphingosine 1 phosphate; Fibrosis; Hypertrophy; PI3K; Protein kinase B/Akt; Ribosomal protein S6; Sphingolipid; mTOR
المشرفين على المادة: 0 (Phosphoinositide-3 Kinase Inhibitors)
0 (Transforming Growth Factor beta)
19794-97-9 (dihydrosphingosine 1-phosphate)
9007-34-5 (Collagen)
EC 2.7.1.1 (mTOR protein, rat)
EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
EC 2.7.11.1 (TOR Serine-Threonine Kinases)
NGZ37HRE42 (Sphingosine)
تواريخ الأحداث: Date Created: 20210220 Date Completed: 20210928 Latest Revision: 20211204
رمز التحديث: 20231215
DOI: 10.1016/j.biocel.2021.105952
PMID: 33609744
قاعدة البيانات: MEDLINE
الوصف
تدمد:1878-5875
DOI:10.1016/j.biocel.2021.105952