دورية أكاديمية
أعرض في EDS

Early life stress induces dysregulation of the heme pathway in adult mice.

التفاصيل البيبلوغرافية
العنوان: Early life stress induces dysregulation of the heme pathway in adult mice.
المؤلفون: Pettway YD; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Neder TH; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Ho DH; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Fox BM; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Burch M; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Colson J; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Liu X; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Kellum CE; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Hyndman KA; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA., Pollock JS; Cardio-Renal Physiology and Medicine, Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
المصدر: Physiological reports [Physiol Rep] 2021 May; Vol. 9 (10), pp. e14844.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society Country of Publication: United States NLM ID: 101607800 Publication Model: Print Cited Medium: Internet ISSN: 2051-817X (Electronic) Linking ISSN: 2051817X NLM ISO Abbreviation: Physiol Rep Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Malden MA] : published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society, 2013-
مواضيع طبية MeSH: Maternal Deprivation* , Weaning*, Heme/*metabolism , Signal Transduction/*physiology , Stress, Psychological/*blood , Stress, Psychological/*psychology, Age Factors ; Animals ; Animals, Newborn ; Endothelium, Vascular/metabolism ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Pregnancy
مستخلص: Early life stress (ELS) is associated with cardiovascular disease (CVD) risk in adulthood, but the underlying vascular mechanisms are poorly understood. Increased hemoglobin and heme have recently been implicated to mediate endothelial dysfunction in several vascular diseases. Chronic physiological stress is associated with alterations in the heme pathway that have been well-described in the literature. However, very little is known about the heme pathway with exposure to ELS or chronic psychosocial stress. Utilizing a mouse model of ELS, maternal separation with early weaning (MSEW), we previously reported that MSEW induces endothelial dysfunction via increased superoxide production. We reasoned that heme dysregulation may be one of the culprits induced by MSEW and sustained throughout adulthood; thus, we hypothesized that MSEW induces heme dysfunction. We investigated whether circulating levels of heme, a circulating pro-oxidant mediator, are increased by MSEW and examined the role of the heme metabolic pathway and heme homeostasis in this process. We found that circulating levels of heme are increased in mice exposed to MSEW and that plasma from MSEW mice stimulated higher superoxide production in cultured mouse aortic endothelial cells (MAECs) compared to plasma from normally reared mice. The heme scavenger hemopexin blunted this enhanced superoxide production. Splenic haptoglobin abundance was significantly lower and hemoglobin levels per red blood cell were significantly higher in MSEW versus control mice. These findings lead us to propose that ELS induces increased circulating heme through dysregulation of the haptoglobin-hemoglobin system representing a mechanistic link between ELS and CVD risk in adulthood.
(© 2021 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)
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معلومات مُعتمدة: P01 HL067669 United States HL NHLBI NIH HHS; R25 DK112731 United States DK NIDDK NIH HHS; K01 DK105038 United States DK NIDDK NIH HHS; R03 DK120503 United States DK NIDDK NIH HHS; R25 GM086256 United States GM NIGMS NIH HHS; F30 DK107194 United States DK NIDDK NIH HHS; T32 DK116672 United States DK NIDDK NIH HHS; P01 HL136267 United States HL NHLBI NIH HHS; U01 HL117684 United States HL NHLBI NIH HHS
فهرسة مساهمة: Keywords: early life stress; haptoglobin; heme; hemoglobin; maternal separation with early weaning; superoxide
المشرفين على المادة: 42VZT0U6YR (Heme)
تواريخ الأحداث: Date Created: 20210527 Date Completed: 20220120 Latest Revision: 20220120
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC8157772
DOI: 10.14814/phy2.14844
PMID: 34042301
قاعدة البيانات: MEDLINE
الوصف
تدمد:2051-817X
DOI:10.14814/phy2.14844