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  1. Article ; Online: Sensational site: the sodium pump ouabain-binding site and its ligands.

    Blaustein, Mordecai P / Hamlyn, John M

    American journal of physiology. Cell physiology

    2024  Volume 326, Issue 4, Page(s) C1120–C1177

    Abstract: Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the mainstay of heart failure (HF) therapy. In the 1950s and 1960s, we learned that the CTS ... ...

    Abstract Cardiotonic steroids (CTS), used by certain insects, toads, and rats for protection from predators, became, thanks to Withering's trailblazing 1785 monograph, the mainstay of heart failure (HF) therapy. In the 1950s and 1960s, we learned that the CTS receptor was part of the sodium pump (NKA) and that the Na
    MeSH term(s) Humans ; Rats ; Animals ; Ouabain/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Ligands ; Digoxin/pharmacology ; Cardiotonic Agents/pharmacology ; Hypertension/drug therapy ; Heart Failure/drug therapy ; Enzyme Inhibitors/pharmacology ; Calcium Signaling ; Binding Sites
    Chemical Substances Ouabain (5ACL011P69) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13) ; Ligands ; Digoxin (73K4184T59) ; Cardiotonic Agents ; Enzyme Inhibitors
    Language English
    Publishing date 2024-01-15
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 392098-7
    ISSN 1522-1563 ; 0363-6143
    ISSN (online) 1522-1563
    ISSN 0363-6143
    DOI 10.1152/ajpcell.00273.2023
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  2. Article ; Online: COVID-19 and Crosstalk With the Hallmarks of Aging.

    Salimi, Shabnam / Hamlyn, John M

    The journals of gerontology. Series A, Biological sciences and medical sciences

    2020  Volume 75, Issue 9, Page(s) e34–e41

    Abstract: Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute ... ...

    Abstract Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen-host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host-coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.
    MeSH term(s) Aged ; Aging/physiology ; Autophagy ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/immunology ; Coronavirus Infections/physiopathology ; Coronavirus Infections/virology ; Epigenesis, Genetic ; Humans ; Immunosenescence ; Mitochondrial Diseases ; Pandemics ; Pneumonia, Viral/immunology ; Pneumonia, Viral/physiopathology ; Pneumonia, Viral/virology ; SARS-CoV-2
    Keywords covid19
    Language English
    Publishing date 2020-06-16
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glaa149
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  3. Article ; Online: Ouabain, endogenous ouabain and ouabain-like factors: The Na

    Blaustein, Mordecai P / Hamlyn, John M

    Cell calcium

    2020  Volume 86, Page(s) 102159

    Abstract: In this brief review we discuss some aspects of the ... ...

    Abstract In this brief review we discuss some aspects of the Na
    MeSH term(s) Animals ; Binding Sites ; Cardiac Glycosides/metabolism ; Humans ; Ouabain/metabolism ; Sodium-Calcium Exchanger/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism
    Chemical Substances Cardiac Glycosides ; Sodium-Calcium Exchanger ; cardiac glycoside receptors ; Ouabain (5ACL011P69) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2020-01-09
    Publishing country Netherlands
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2020.102159
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  4. Article ; Online: Essential contributions of the α2-Na

    Blaustein, Mordecai P / Hamlyn, John M / Leenen, Frans H H

    American journal of physiology. Heart and circulatory physiology

    2021  Volume 321, Issue 6, Page(s) H1117–H1118

    MeSH term(s) Binding Sites ; Humans ; Ouabain ; Protein Binding ; Sodium-Potassium-Exchanging ATPase/metabolism ; Ventricular Remodeling
    Chemical Substances Ouabain (5ACL011P69) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2021-11-29
    Publishing country United States
    Document type Letter ; Comment
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00548.2021
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  5. Article: Natriuretic hormones, endogenous ouabain, and related sodium transport inhibitors.

    Hamlyn, John M

    Frontiers in endocrinology

    2014  Volume 5, Page(s) 199

    Abstract: The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NHs). In addition to the atrial peptides (APs), the circulation contains unidentified physiologically relevant NHs. One NH is controlled by the central ... ...

    Abstract The work of deWardener and colleagues stimulated longstanding interest in natriuretic hormones (NHs). In addition to the atrial peptides (APs), the circulation contains unidentified physiologically relevant NHs. One NH is controlled by the central nervous system (CNS) and likely secreted by the pituitary. Its circulating activity is modulated by salt intake and the prevailing sodium concentration of the blood and intracerebroventricular fluid, and contributes to postprandial and dehydration natriuresis. The other NH, mobilized by atrial stretch, promotes natriuresis by increasing the production of intrarenal dopamine and/or nitric oxide (NO). Both NHs have short (<35 min) circulating half lives, depress renotubular sodium transport, and neither requires the renal nerves. The search for NHs led to endogenous cardiotonic steroids (CTS) including ouabain-, digoxin-, and bufadienolide-like materials. These CTS, given acutely in high nanomole to micromole amounts into the general or renal circulations, inhibit sodium pumps and are natriuretic. Among these CTS, only bufalin is cleared sufficiently rapidly to qualify for an NH-like role. Ouabain-like CTS are cleared slowly, and when given chronically in low daily nanomole amounts, promote sodium retention, augment arterial myogenic tone, reduce renal blood flow and glomerular filtration, suppress NO in the renal vasa recta, and increase sympathetic nerve activity and blood pressure. Moreover, lowering total body sodium raises circulating endogenous ouabain. Thus, ouabain-like CTS have physiological actions that, like aldosterone, support renal sodium retention and blood pressure. In conclusion, the mammalian circulation contains two non-AP NHs. Identification of the CNS NH should be a priority.
    Language English
    Publishing date 2014
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2592084-4
    ISSN 1664-2392
    ISSN 1664-2392
    DOI 10.3389/fendo.2014.00199
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  6. Article ; Online: COVID-19 and Crosstalk With the Hallmarks of Aging

    Salimi, Shabnam / Hamlyn, John M

    The Journals of Gerontology: Series A

    2020  Volume 75, Issue 9, Page(s) e34–e41

    Abstract: Abstract Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe ...

    Abstract Abstract Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.
    Keywords Ageing ; Geriatrics and Gerontology ; covid19
    Language English
    Publisher Oxford University Press (OUP)
    Publishing country uk
    Document type Article ; Online
    ZDB-ID 1223643-3
    ISSN 1758-535X ; 1079-5006
    ISSN (online) 1758-535X
    ISSN 1079-5006
    DOI 10.1093/gerona/glaa149
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article: COVID-19 and Crosstalk With the Hallmarks of Aging

    Salimi, Shabnam / Hamlyn, John M

    J Gerontol A Biol Sci Med Sci

    Abstract: Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute ... ...

    Abstract Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen-host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging, coupled with host-coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, epigenetic alterations, telomere attrition, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of antiaging drug candidates that require paramount attention in COVID-19 research.
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #599215
    Database COVID19

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  8. Article ; Online: Whither digitalis? What we can still learn from cardiotonic steroids about heart failure and hypertension.

    Blaustein, Mordecai P / Gottlieb, Stephen S / Hamlyn, John M / Leenen, Frans H H

    American journal of physiology. Heart and circulatory physiology

    2022  Volume 323, Issue 6, Page(s) H1281–H1295

    Abstract: Cloning of the " ... ...

    Abstract Cloning of the "Na
    MeSH term(s) Digitalis ; Cardiac Glycosides ; Ligands ; Heart Failure/drug therapy ; Hypertension/drug therapy
    Chemical Substances Cardiac Glycosides ; Ligands
    Language English
    Publishing date 2022-11-11
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 603838-4
    ISSN 1522-1539 ; 0363-6135
    ISSN (online) 1522-1539
    ISSN 0363-6135
    DOI 10.1152/ajpheart.00362.2022
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  9. Article ; Online: Sodium pumps, ouabain and aldosterone in the brain: A neuromodulatory pathway underlying salt-sensitive hypertension and heart failure.

    Leenen, Frans H H / Wang, Hong-Wei / Hamlyn, John M

    Cell calcium

    2019  Volume 86, Page(s) 102151

    Abstract: Accumulating evidence obtained over the last three decades has revealed a neuroendocrine system in the brain that mediates long term increases in blood pressure. The system involves distinct ion transport pathways including the alpha-2 isoform of the Na, ... ...

    Abstract Accumulating evidence obtained over the last three decades has revealed a neuroendocrine system in the brain that mediates long term increases in blood pressure. The system involves distinct ion transport pathways including the alpha-2 isoform of the Na,K pump and epithelial sodium channels, as well as critical hormone elements such as angiotensin II, aldosterone, mineralocorticoid receptors and endogenous ouabain. Activation of this system either by circulating or central sodium ions and/or angiotensin II leads to a cascading sequence of events that begins in the hypothalamus and involves the participation of several brain nuclei including the subfornical organ, supraoptic and paraventricular nuclei and the rostral ventral medulla. Key events include heightened aldosterone synthesis and mineralocorticoid receptor activation, upregulation of epithelial sodium channels, augmented synthesis and secretion of endogenous ouabain from hypothalamic magnocellular neurons, and sustained increases in sympathetic outflow. The latter step depends upon increased production of angiotensin II and the primary amplification of angiotensin II type I receptor signaling from the paraventricular nucleus to the rostral ventral lateral medulla. The transmission of sympathetic traffic is secondarily amplified in the periphery by increased short- and long-term potentiation in sympathetic ganglia and by sustained actions of endogenous ouabain in the vascular wall that augment expression of sodium calcium exchange, increase cytosolic Ca
    MeSH term(s) Aldosterone/metabolism ; Animals ; Brain/metabolism ; Heart Failure/blood ; Heart Failure/complications ; Heart Failure/metabolism ; Heart Failure/physiopathology ; Humans ; Hypertension/blood ; Hypertension/complications ; Hypertension/metabolism ; Hypertension/physiopathology ; Ouabain/blood ; Ouabain/metabolism ; Sodium Chloride, Dietary/adverse effects ; Sodium-Potassium-Exchanging ATPase/metabolism
    Chemical Substances Sodium Chloride, Dietary ; Aldosterone (4964P6T9RB) ; Ouabain (5ACL011P69) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2019-12-17
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 757687-0
    ISSN 1532-1991 ; 0143-4160
    ISSN (online) 1532-1991
    ISSN 0143-4160
    DOI 10.1016/j.ceca.2019.102151
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  10. Article ; Online: Endogenous Ouabain: Recent Advances and Controversies.

    Hamlyn, John M / Blaustein, Mordecai P

    Hypertension (Dallas, Tex. : 1979)

    2016  Volume 68, Issue 3, Page(s) 526–532

    Language English
    Publishing date 2016-09
    Publishing country United States
    Document type Journal Article
    ZDB-ID 423736-5
    ISSN 1524-4563 ; 0194-911X ; 0362-4323
    ISSN (online) 1524-4563
    ISSN 0194-911X ; 0362-4323
    DOI 10.1161/HYPERTENSIONAHA.116.06599
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