Abscisic Acid: A New Mammalian Hormone Regulating Glucose Homeostasis

Bruzzone, Santina; Ameri, Pietro; Sturla, Laura; Guida, Lucrezia; Flora, Antonio De; Zocchi, Elena

doi:10.1166/msr.2012.1012

Cited by 6 publications

(9 citation statements)

References 30 publications

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“…Concerning the mechanisms of ABA release in mammalian cells, it has been reported recently that ABA transport is mediated by members of the anion exchanger (AE) family of anion exchangers and is bidirectional (41,42). This feature accounts for ABA uptake and release from mammalian and human cells and, more generally, for the mechanisms of ABArelated autocrine and paracrine functions in the animal kingdom (43). Established sources of plasmatic ABA, in addition to dietary intake of fruits and vegetables (10), are pancreatic ␤ cells, adipocytes, and, to a lesser extent, granulocytes, monocytes, and mesenchymal stem cells (43).…”

Section: Discussionmentioning

confidence: 99%

“…This feature accounts for ABA uptake and release from mammalian and human cells and, more generally, for the mechanisms of ABArelated autocrine and paracrine functions in the animal kingdom (43). Established sources of plasmatic ABA, in addition to dietary intake of fruits and vegetables (10), are pancreatic ␤ cells, adipocytes, and, to a lesser extent, granulocytes, monocytes, and mesenchymal stem cells (43).…”

Section: Discussionmentioning

confidence: 99%

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The Plant Hormone Abscisic Acid Is a Prosurvival Factor in Human and Murine Megakaryocytes

Malara

Fresia

Buduo

et al. 2017

Journal of Biological Chemistry

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Abscisic acid (ABA) is a phytohormone involved in pivotal physiological functions in higher plants. Recently, ABA has been proven to be also secreted and active in mammals, where it stimulates the activity of innate immune cells, mesenchymal and hematopoietic stem cells, and insulin-releasing pancreatic β cells through a signaling pathway involving the second messenger cyclic ADP-ribose (cADPR). In addition to behaving like an animal hormone, ABA also holds promise as a nutraceutical plant-derived compound in humans. Many biological functions of ABA in mammals are mediated by its binding to the LANCL-2 receptor protein. A putative binding of ABA to GRP78, a key regulator of endoplasmic reticulum stress, has also been proposed. Here we investigated the role of exogenous ABA in modulating thrombopoiesis, the process of platelet generation. Our results demonstrate that expression of both LANCL-2 and GRP78 is up-regulated during hematopoietic stem cell differentiation into mature megakaryocytes (Mks). Functional ABA receptors exist in mature Mks because ABA induces an intracellular Ca increase ([Ca] ) through PKA activation and subsequent cADPR generation. exposure of human or murine hematopoietic progenitor cells to 10 μm ABA does not increase recombinant thrombopoietin (rTpo)-dependent Mk differentiation or platelet release. However, under conditions of cell stress induced by rTpo and serum deprivation, ABA stimulates, in a PKA- and cADPR-dependent fashion, the mitogen-activated kinase ERK 1/2, resulting in the modulation of lymphoma 2 (Bcl-2) family members, increased Mk survival, and higher rates of platelet production. In conclusion, we demonstrate that ABA is a prosurvival factor for Mks in a Tpo-independent manner.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

The Plant Hormone Abscisic Acid Is a Prosurvival Factor in Human and Murine Megakaryocytes

Malara

Fresia

Buduo

et al. 2017

Journal of Biological Chemistry

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“…ABA is a hormone shared by plants and animals, with a conserved role as a stress signal that regulates cell responses to environmental stimuli (15)(16)(17). This singular, up to now unique, feature of this hormone should enable in principle the replenishment of endogenous ABA insufficiency with exogenous plantderived hormone.…”

Section: Discussionmentioning

confidence: 99%

Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans

et al. 2015

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2-Cis,4-trans-abscisic acid (ABA) is a plant hormone that is present also in animals. Several lines of evidence suggest that ABA contributes to the regulation of glycemia in mammals: nanomolar ABA stimulates insulin release from b-pancreatic cells and glucose transporter-4-mediated glucose uptake by myoblasts and adipocytes in vitro; plasma ABA increases in normal human subjects, but not in diabetic patients, after a glucose load for an oral glucose tolerance test (OGTT). The presence of ABA in fruits prompted an exploration of the bioavailability of dietary ABA and the effect of ABA-rich fruit extracts on glucose tolerance. Rats underwent an OGTT, with or without 1 mg/kg ABA, either synthetic or present in a fruit extract. Human volunteers underwent an OGTT or a standard breakfast and lunch, with or without a fruit extract, yielding an ABA dose of 0.85 or 0.5 mg/kg, respectively. Plasma glucose, insulin, and ABA were measured at different time points. Oral ABA at 0.5-1 mg/kg significantly lowered glycemia and insulinemia in rats and in humans. Thus, the glycemia-lowering effect of low-dose

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“…LANCL1 has been hypothesized to be implicated in the metabolism of lanthionine metabolites in the central nervous system 4 . LANCL2 proved to be the human receptor of abscisic acid (ABA) 5 6 7 8 9 10 .…”

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G-protein coupling and nuclear translocation of the human abscisic acid receptor LANCL2

Fresia

Vigliarolo

Guida

et al. 2016

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Abscisic acid (ABA), a long known phytohormone, has been recently demonstrated to be present also in humans, where it targets cells of the innate immune response, mesenchymal and hemopoietic stem cells and cells involved in the regulation of systemic glucose homeostasis. LANCL2, a peripheral membrane protein, is the mammalian ABA receptor. We show that N-terminal glycine myristoylation causes LANCL2 localization to the plasmamembrane and to cytoplasmic membrane vesicles, where it interacts with the α subunit of a Gi protein and starts the ABA signaling pathway via activation of adenylate cyclase. Demyristoylation of LANCL2 by chemical or genetic means triggers its nuclear translocation. Nuclear enrichment of native LANCL2 is also induced by ABA treatment. Therefore human LANCL2 is a non-transmembrane G protein-coupled receptor susceptible to hormone-induced nuclear translocation.

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Abscisic Acid: A New Mammalian Hormone Regulating Glucose Homeostasis

Cited by 6 publications

References 30 publications

The Plant Hormone Abscisic Acid Is a Prosurvival Factor in Human and Murine Megakaryocytes

The Plant Hormone Abscisic Acid Is a Prosurvival Factor in Human and Murine Megakaryocytes

Microgram amounts of abscisic acid in fruit extracts improve glucose tolerance and reduce insulinemia in rats and in humans

G-protein coupling and nuclear translocation of the human abscisic acid receptor LANCL2

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