دورية أكاديمية
أعرض في EDS

ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload.

التفاصيل البيبلوغرافية
العنوان: ER calcium release promotes mitochondrial dysfunction and hepatic cell lipotoxicity in response to palmitate overload.
المؤلفون: Egnatchik RA; Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Leamy AK; Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA., Jacobson DA; Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Shiota M; Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA., Young JD; Chemical and Biomolecular Engineering, Vanderbilt University, Nashville, TN, USA ; Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN, USA.
المصدر: Molecular metabolism [Mol Metab] 2014 May 22; Vol. 3 (5), pp. 544-53. Date of Electronic Publication: 2014 May 22 (Print Publication: 2014).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier GmbH Country of Publication: Germany NLM ID: 101605730 Publication Model: eCollection Cited Medium: Print ISSN: 2212-8778 (Print) Linking ISSN: 22128778 NLM ISO Abbreviation: Mol Metab Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: [München] : Elsevier GmbH, 2012-
مستخلص: Palmitate overload induces hepatic cell dysfunction characterized by enhanced apoptosis and altered citric acid cycle (CAC) metabolism; however, the mechanism of how this occurs is incompletely understood. We hypothesize that elevated doses of palmitate disrupt intracellular calcium homeostasis resulting in a net flux of calcium from the ER to mitochondria, activating aberrant oxidative metabolism. We treated primary hepatocytes and H4IIEC3 cells with palmitate and calcium chelators to identify the roles of intracellular calcium flux in lipotoxicity. We then applied (13)C metabolic flux analysis (MFA) to determine the impact of calcium in promoting palmitate-stimulated mitochondrial alterations. Co-treatment with the calcium-specific chelator BAPTA resulted in a suppression of markers for apoptosis and oxygen consumption. Additionally, (13)C MFA revealed that BAPTA co-treated cells had reduced CAC fluxes compared to cells treated with palmitate alone. Our results demonstrate that palmitate-induced lipoapoptosis is dependent on calcium-stimulated mitochondrial activation, which induces oxidative stress.
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معلومات مُعتمدة: K01 DK081666 United States DK NIDDK NIH HHS; P30 DK020593 United States DK NIDDK NIH HHS; P60 DK020593 United States DK NIDDK NIH HHS
فهرسة مساهمة: Keywords: APE, atom percent enrichment; BSA, bovine serum albumin; CAC, citric acid cycle; ER stress; FFA, free fatty acid; Fatty liver; GC–MS, gas chromatography–mass spectrometry; H2DCFDA, 2′,7′-dichlorodihydrofluorescein diacetate; Lipotoxicity; MFA, metabolic flux analysis; MUFA, monounsaturated fatty acid; Metabolic flux analysis; NAFLD, non-alcoholic fatty liver disease; NASH, non-alcoholic steatohepatitis; OA, oleate; Oxidative stress; PA, palmitate; PI, propidium iodide; ROS, reactive oxygen species; SERCA, sarcoplasmic-endoplasmic reticulum calcium ATPase; SFA, saturated fatty acid
تواريخ الأحداث: Date Created: 20140726 Date Completed: 20140725 Latest Revision: 20211021
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4099508
DOI: 10.1016/j.molmet.2014.05.004
PMID: 25061559
قاعدة البيانات: MEDLINE
الوصف
تدمد:2212-8778
DOI:10.1016/j.molmet.2014.05.004