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J Biol Chem. 2017 Feb 24;292(8):3239-3251. doi: 10.1074/jbc.M116.751693. Epub 2017 Jan 3.

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

Author information

1
From the Departments of Molecular Medicine, Laboratories of Biotechnology, IRCCS San Matteo Foundation, and.
2
the Department of Experimental Medicine, Section of Biochemistry, University of Genova, Genova 16132, Italy, and.
3
Biology and Biotechnology, University of Pavia, Pavia 27100, Italy.
4
From the Departments of Molecular Medicine, Laboratories of Biotechnology, IRCCS San Matteo Foundation, and alessandra.balduini@unipv.it.
5
the Department of Biomedical Engineering, Tufts University, Medford, Massachusetts 02155.

Abstract

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 Ca2+ increase ([Ca2+] i ) through PKA activation and subsequent cADPR generation. In vitro 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.

KEYWORDS:

B cell lymphoma 2 (Bcl-2) family; ERK; PKA; abscisic acid (ABA); calcium; cyclic ADP Ribose (cADPR); megakaryocyte; thrombopoiesis

PMID:
28049729
PMCID:
PMC5336159
DOI:
10.1074/jbc.M116.751693
[Indexed for MEDLINE]
Free PMC Article

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