Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ

Bassaganya‐Riera, Josep; Guri, Amir J.; Lu, Pinyi; Climent, Montserrat; Carbo, Adria; Sobral, Bruno W. S.; Horne, William; Lewis, Stephanie N.; Bevan, David R.; Hontecillas, Raquel

doi:10.1074/jbc.m110.160077

Cited by 106 publications

(136 citation statements)

References 61 publications

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“…In particular, ABA stimulates insulin release in a glucose concentration-dependent manner 48 and can enhance or suppress nuclear factor-kappa B (NF-κB) activity depending on cell type. 49 Here, we speculate that the reduction in pathology in our mouse model is likely due to a combination of the direct effects of ABA on host tissues and the reduction in parasitemia.…”

Section: Discussionmentioning

confidence: 99%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Nearly half of the world's population is at risk for malaria. Increasing drug resistance has intensified the need for novel therapeutics, including treatments with intrinsic transmission-blocking properties. In this study, we demonstrate that the isoprenoid abscisic acid (ABA) modulates signaling in the mammalian host to reduce parasitemia and the formation of transmissible gametocytes and in the mosquito host to reduce parasite infection. Oral ABA supplementation in a mouse model of malaria was well tolerated and led to reduced pathology and enhanced gene expression in the liver and spleen consistent with infection recovery. Oral ABA supplementation also increased mouse plasma ABA to levels that can signal in the mosquito midgut upon blood ingestion. Accordingly, we showed that supplementation of a Plasmodium falciparum-infected blood meal with ABA increased expression of mosquito nitric oxide synthase and reduced infection prevalence in a nitric oxide-dependent manner. Identification of the mechanisms whereby ABA reduces parasite growth in mammals and mosquitoes could shed light on the balance of immunity and metabolism across eukaryotes and provide a strong foundation for clinical translation.

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Section: Discussionmentioning

confidence: 99%

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Glennon¹,

Adams²,

Hicks³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…In animals, ABA has been shown to stimulate a sustained Ca 2? response via cyclic ADP-ribose (cADPR) (Puce et al 2004;Bruzzone et al 2007;Bassaganya-Riera et al 2010). ABA signaling cascade in angiosperms is also proposed to involve cADPR and Ca 2?…”

Section: Metazoan Animalsmentioning

confidence: 98%

ABA in bryophytes: how a universal growth regulator in life became a plant hormone?

2011

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Abscisic acid (ABA) is not a plant-specific compound but one found in organisms across kingdoms from bacteria to animals, suggesting that it is a ubiquitous and versatile substance that can modulate physiological functions of various organisms. Recent studies have shown that plants developed an elegant system for ABA sensing and early signal transduction mechanisms to modulate responses to environmental stresses for survival in terrestrial conditions. ABA-induced increase in stress tolerance has been reported not only in vascular plants but also in non-vascular bryophytes. Since bryophytes are the key group of organisms in the context of plant evolution, clarification of their ABA-dependent processes is important for understanding evolutionary adaptation of land plants. Molecular approaches using Physcomitrella patens have revealed that ABA plays a role in dehydration stress tolerance in mosses, which comprise a major group of bryophytes. Furthermore, we recently reported that signaling machinery for ABA responses is also conserved in liverworts, representing the most basal members of extant land plant lineage. Conservation of the mechanism for ABA sensing and responses in angiosperms and basal land plants suggests that acquisition of this mechanism for stress tolerance in vegetative tissues was one of the critical evolutionary events for adaptation to the land. This review describes the role of ABA in basal land plants as well as non-land plant organisms and further elaborates on recent progress in molecular studies of model bryophytes by comparative and functional genomic approaches.

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“…Endogenously produced ABA is proposed to act locally and in the case of pancreatic β-cells has been shown to enhance their ability to secrete insulin (18). ABA is also involved in various immune and inflammatory responses, and has been administrated orally in mouse models to treat diabetes, 5 atherosclerosis and inflammatory bowel disease (14,(19)(20)(21). However, some contradictory reports do exist, related to the effect of ABA on Ca 2+ responses in microglial cells (22).…”

mentioning

confidence: 99%

Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4

et al. 2015

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Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to the oral cavity, T2Rs are expressed in many extraoral tissues, including the central nervous system, respiratory system, and reproductive system. To understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel blockers or antagonists are urgently needed. Recently, we elucidated the binding pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory neurotransmitter, γ-aminobutyric acid. This structure-function information about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor (xanthoxin), and catabolite phaseic acid for their ability to bind and activate or inhibit T2R4. Molecular docking studies followed by functional assays involving calcium imaging confirmed that ABA is an antagonist with an IC50 value of 34.4 ± 1.1 μM. However, ABA precursor xanthoxin acts as an agonist on T2R4. Interestingly, molecular model-guided site-directed mutagenesis suggests that the T2R4 residues involved in quinine binding are also predominantly involved in binding to the novel antagonist, ABA. The antagonist ability of ABA was tested using another T2R4 agonist, yohimbine. Our results suggest that ABA does not inhibit yohimbine-induced T2R4 activity. The discovery of natural bitter blockers has immense nutraceutical and physiological significance and will help in dissecting the T2R molecular pathways in various tissues.

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Abscisic Acid Regulates Inflammation via Ligand-binding Domain-independent Activation of Peroxisome Proliferator-activated Receptor γ

Cited by 106 publications

References 61 publications

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

Supplementation with Abscisic Acid Reduces Malaria Disease Severity and Parasite Transmission

ABA in bryophytes: how a universal growth regulator in life became a plant hormone?

Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4

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