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1.
Microbiol Res ; 287: 127868, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39126862

ABSTRACT

Pseudomonas protegens can generally produce multiple antibiotics including pyoluteorin (Plt), 2,4-diacetylphloroglucinol (DAPG), and pyrrolnitrin (Prn). In this study, we discovered and characterized a quorum sensing (QS) system, PpqI/R, in P. protegens H78. PpqI/R, encoded by two open reading frames (ORFs) (H78_01960/01961) in P. protegens H78 genome, is a LuxI/R-type QS system. Four long-chain acyl homoserine lactone (AHL) signaling molecules, 3-OH-C10-HSL, 3-OH-C12-HSL, C12-HSL, and 3-OH-C14-HSL, are produced by H78. Biosynthesis of these AHLs is catalyzed by PpqI synthase and activated by the PpqR regulator in H78 and in Escherichia coli when heterologously expressed. PpqR activates ppqI expression by targeting the lux box upstream of the ppqI promoter in cooperation with corresponding AHLs. The four aforementioned AHLs exhibited different capabilities to induce ppqI promoter expression, with 3-OH-C12-HSL showing the highest induction activity. In H78 cells, ppqI/R expression is activated by the two-component system GacS/A and the RNA chaperone Hfq. Differential regulation of the PpqI/R system in secondary metabolism has a negative effect on DAPG biosynthesis and ped operon (involved in volatile organic compound biosynthesis) expression. In contrast, Plt biosynthesis and prn operon expression were positively regulated by PpqI/R. In summary, PpqI/R, the first characterized QS system in P. protegens, is activated by GacS/A and Hfq and controls the expression of secondary metabolites, including antibiotics.


Subject(s)
Bacterial Proteins , Gene Expression Regulation, Bacterial , Pseudomonas , Quorum Sensing , Quorum Sensing/genetics , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Pseudomonas/metabolism , Pseudomonas/genetics , Host Factor 1 Protein/metabolism , Host Factor 1 Protein/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Phloroglucinol/metabolism , Phloroglucinol/analogs & derivatives , Acyl-Butyrolactones/metabolism , Phenols/metabolism , Pyrrolnitrin/metabolism , Pyrroles/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Open Reading Frames , Promoter Regions, Genetic , Heterocyclic Compounds, 3-Ring/metabolism
2.
Plant Physiol Biochem ; 215: 109054, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39163653

ABSTRACT

Strigolactone (SL), a plant hormone derived from carotenoids, has been recognized for its pivotal role in regulating plant growth. Nevertheless, the influence of SL on tall fescue (Festuca arundinacea) under low-light conditions remains unclear. This study aimed to investigate the impact of SL on various aspects of tall fescue, including its morphological characteristics, photosynthesis, levels of antioxidant and concentrations of SL, under low light intensity (LI). The findings showed that GR24, an artificial analog of SL, positively influenced several parameters of tall fescue under LI. In particular, it enhanced the morphological features such as plant height, leaf width, and biomass, while reducing the number of tillers. Furthermore, it improved the efficiency of photosynthetic by enhancing chlorophyll fluorescence and the gas exchange parameters, mitigating cell damage and improving the contents of antioxidants by increasing the levels of antioxidant enzymes and non-enzymatic antioxidant compounds. Moreover, treatment with SL led to elevated concentrations of this hormone and the levels of gene expression in related pathways. Owing to the immaturity of the genetic transformation system in tall fescue, partial validation through transgenic and mutant materials was obtained using Arabidopsis (Arabidopsis thaliana). These findings demonstrate that SL alleviates the physiological indicators of tall fescue under LI stress and enhances its tolerance to shade. Additionally, it suggests that SL may regulate the shade tolerance of tall fescue through the involvement of FaD14.


Subject(s)
Festuca , Lactones , Light , Photosynthesis , Lactones/metabolism , Festuca/metabolism , Festuca/radiation effects , Festuca/genetics , Festuca/growth & development , Arabidopsis/metabolism , Arabidopsis/genetics , Arabidopsis/radiation effects , Antioxidants/metabolism , Stress, Physiological , Plant Growth Regulators/metabolism , Gene Expression Regulation, Plant , Heterocyclic Compounds, 3-Ring/metabolism , Chlorophyll/metabolism
3.
Sci Rep ; 14(1): 16290, 2024 07 15.
Article in English | MEDLINE | ID: mdl-39009738

ABSTRACT

Bictegravir, a key second-generation integrase strand transfer inhibitor in the treatment of HIV, is subject to active efflux transport mediated by ABCB1 (P-glycoprotein). Several coding variants of ABCB1 have been described and associated with variable effects on substrate drugs pharmacokinetics. Here, we investigated the effect of the four most common coding ABCB1 single nucleotide polymorphisms (i.e., c.1199G > A, c.1236C > T, c.2677G > T and c.3435C > T) on the intracellular accumulation of bictegravir. Using a previously validated HEK293 recombinant cell line model, we found decreased bictegravir intracellular concentrations in cell lines overexpressing ABCB1 as compared to control cell lines, in line with the known role of ABCB1 in bictegravir transport. However, we were unable to demonstrate any significant difference in bictegravir intracellular accumulation when comparing HEK293 cells overexpressing the wild type (1236C-2677G-3435C, 1199G) or the variant (1236C-2677G-3435T, 1236T-2677T-3435T or 1199A) proteins. These findings suggest that the ABCB1 c.1199G > A and c.1236C > T-c.2677G > T-c.3435C > T variants have no or at least limited impact on the active transport of bictegravir by ABCB1.


Subject(s)
ATP Binding Cassette Transporter, Subfamily B , Piperazines , Polymorphism, Single Nucleotide , Humans , HEK293 Cells , ATP Binding Cassette Transporter, Subfamily B/genetics , ATP Binding Cassette Transporter, Subfamily B/metabolism , Piperazines/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Amides/metabolism , Pyridones/metabolism , Heterocyclic Compounds, 4 or More Rings/metabolism
4.
Plant Cell ; 36(10): 4404-4425, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-38917246

ABSTRACT

Although the strigolactone (SL) signaling pathway and SL-mediated anthocyanin biosynthesis have been reported, the molecular association between SL signaling and anthocyanin biosynthesis remains unclear. In this study, we identified the SL signal transduction pathway associated with anthocyanin biosynthesis and the crosstalk between gibberellin (GA) and SL signaling in apple (Malus × domestica). ELONGATED HYPOCOTYL5 (HY5) acts as a key node integrating SL signaling and anthocyanin biosynthesis, and the SL-response factor AGAMOUS-LIKE MADS-BOX9 (AGL9) promotes anthocyanin biosynthesis by activating HY5 transcription. The SL signaling repressor SUPPRESSOR OF MAX2 1-LIKE8 (SMXL8) interacts with AGL9 to form a complex that inhibits anthocyanin biosynthesis by downregulating HY5 expression. Moreover, the E3 ubiquitin ligase PROTEOLYSIS1 (PRT1) mediates the ubiquitination-mediated degradation of SMXL8, which is a key part of the SL signal transduction pathway associated with anthocyanin biosynthesis. In addition, the GA signaling repressor REPRESSOR-of-ga1-3-LIKE2a (RGL2a) mediates the crosstalk between GA and SL by disrupting the SMXL8-AGL9 interaction that represses HY5 transcription. Taken together, our study reveals the regulatory mechanism of SL-mediated anthocyanin biosynthesis and uncovers the role of SL-GA crosstalk in regulating anthocyanin biosynthesis in apple.


Subject(s)
Anthocyanins , Gene Expression Regulation, Plant , Gibberellins , Lactones , Malus , Plant Proteins , Malus/metabolism , Malus/genetics , Anthocyanins/metabolism , Gibberellins/metabolism , Lactones/metabolism , Plant Proteins/metabolism , Plant Proteins/genetics , Signal Transduction , Heterocyclic Compounds, 3-Ring/metabolism
5.
Plant J ; 119(3): 1526-1542, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38858857

ABSTRACT

Strigolactones (SL) function as plant hormones in control of multiple aspects of plant development, mostly via the regulation of gene expression. Immediate early-gene regulation by SL remains unexplored due to difficulty in dissecting early from late gene expression responses to SL. We used synthetic SL, rac-GR24 treatment of protoplasts and RNA-seq to explore early SL-induced changes in gene expression over time (5-180 minutes) and discovered rapid, dynamic and SL receptor D14-dependent regulation of gene expression in response to rac-GR24. Importantly, we discovered a significant dependence of SL signalling on chromatin remodelling processes, as the induction of a key SL-induced transcription factor BRANCHED1 requires the SWI/SNF chromatin remodelling ATPase SPLAYED (SYD) and leads to upregulation of a homologue SWI/SNF ATPase BRAHMA. ATAC-seq profiling of genome-wide changes in chromatin accessibility in response to rac-GR24 identified large-scale changes, with over 1400 differentially accessible regions. These changes in chromatin accessibility often precede transcriptional changes and are likely to harbour SL cis-regulatory elements. Importantly, we discovered that this early and extensive modification of the chromatin landscape also requires SYD. This study, therefore, provides evidence that SL signalling requires regulation of chromatin accessibility, and it identifies genomic locations harbouring likely SL cis-regulatory sequences.


Subject(s)
Chromatin Assembly and Disassembly , Gene Expression Regulation, Plant , Lactones , Plant Growth Regulators , Lactones/metabolism , Plant Growth Regulators/metabolism , Transcription Factors/metabolism , Transcription Factors/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Arabidopsis Proteins/genetics , Arabidopsis Proteins/metabolism , Chromatin/metabolism , Chromatin/genetics , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , Signal Transduction
6.
Plant J ; 119(1): 197-217, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38565306

ABSTRACT

Poor management and excess fertilization of apple (Malus domestica Borkh.) orchards are causing increasingly serious soil acidification, resulting in Al toxicity and direct poisoning of roots. Strigolactones (SLs) are reported to be involved in plant responses to abiotic stress, but their role and mechanism under AlCl3 stress remain unknown. Here, we found that applying 1 µm GR24 (an SL analoge) significantly alleviated AlCl3 stress of M26 apple rootstock, mainly by blocking the movement of Al through cell wall and by vacuolar compartmentalization of Al. RNA-seq analysis identified the core transcription factor gene MdWRKY53, and overexpressing MdWRKY53 enhanced AlCl3 tolerance in transgenic apple plants through the same mechanism as GR24. Subsequently, we identified MdPMEI45 (encoding pectin methylesterase inhibitor) and MdALS3 (encoding an Al transporter) as downstream target genes of MdWRKY53 using chromatin immunoprecipitation followed by sequencing (ChIP-seq). GR24 enhanced the interaction between MdWRKY53 and the transcription factor MdTCP15, further increasing the binding of MdWRKY53 to the MdPMEI45 promoter and inducing MdPMEI45 expression to prevent Al from crossing cell wall. MdWRKY53 also bound to the promoter of MdALS3 and enhanced its transcription to compartmentalize Al in vacuoles under AlCl3 stress. We therefore identified two modules involved in alleviating AlCl3 stress in woody plant apple: the SL-WRKY+TCP-PMEI module required for excluding external Al by blocking the entry of Al3+ into cells and the SL-WRKY-ALS module allowing internal detoxification of Al through vacuolar compartmentalization. These findings lay a foundation for the practical application of SLs in agriculture.


Subject(s)
Aluminum Chloride , Cell Wall , Gene Expression Regulation, Plant , Malus , Plant Proteins , Vacuoles , Malus/genetics , Malus/metabolism , Malus/drug effects , Vacuoles/metabolism , Cell Wall/metabolism , Cell Wall/drug effects , Plant Proteins/genetics , Plant Proteins/metabolism , Gene Expression Regulation, Plant/drug effects , Lactones/metabolism , Lactones/pharmacology , Plants, Genetically Modified , Stress, Physiological , Plant Roots/metabolism , Plant Roots/genetics , Plant Roots/drug effects , Heterocyclic Compounds, 3-Ring/metabolism , Heterocyclic Compounds, 3-Ring/pharmacology , Transcription Factors/metabolism , Transcription Factors/genetics , Promoter Regions, Genetic
7.
BMC Plant Biol ; 24(1): 320, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38654155

ABSTRACT

BACKGROUND: As a newly class of endogenous phytohormones, strigolactones (SLs) regulate crop growth and yield formation by interacting with other hormones. However, the physiological mechanism of SLs affect the yield by regulating the balance of endogenous hormones of Tartary buckwheat is still unclear. RESULTS: In this study, a 2-year field experiment was conducted on Tartary buckwheat (Jinqiao 2) to study the effects of different concentrations (0, 10, and 20 µmol/L) of artificial synthetic analogs of SLs (rac-GR24) and inhibitor of SL synthesis (Tis-108) on the growth, endogenous-hormone content, and yield of Tartary buckwheat. The main-stem branch number, grain number per plant, grain weight per plant, and yield of Tartary buckwheat continuously decreased with increased rac-GR24 concentration, whereas the main-stem diameter and plant height initially increased and then decreased. Rac-GR24 treatment significantly increased the content of SLs and abscisic acid (ABA) in grains, and it decreased the content of Zeatin (Z) + Zeatin nucleoside (ZR). Conversely, Tis-108 treatment decreased the content of SLs and ABA but increased the content of Z + ZR. Results of correlation analysis showed that the content of ABA and SLs, the ratio of SLs/(Z + ZR), SLs/ABA, and ABA/(Z + ZR) were significantly negatively correlated with the yield of Tartary buckwheat, and that Z + ZR content was significantly positively correlated with the yield. Regression analysis further showed that ABA/ (Z + ZR) can explain 58.4% of the variation in yield. CONCLUSIONS: In summary, by adjusting the level of endogenous SLs in Tartary buckwheat, the balance of endogenous hormones in grains can be changed, thereby exerting the effect on yield. The results can provide a new agronomic method for the high-yield cultivation of Tartary buckwheat.


Subject(s)
Fagopyrum , Lactones , Plant Growth Regulators , Fagopyrum/drug effects , Fagopyrum/growth & development , Fagopyrum/metabolism , Plant Growth Regulators/metabolism , Plant Growth Regulators/pharmacology , Lactones/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Abscisic Acid/metabolism
8.
J Phys Chem B ; 128(3): 698-705, 2024 Jan 25.
Article in English | MEDLINE | ID: mdl-38194306

ABSTRACT

The parasitic plant witchweed, Striga hermonthica, results in agricultural losses of billions of dollars per year. It perceives its host via plant hormones called strigolactones, which act as germination stimulants for witchweed. Strigolactone signaling involves substrate binding to the strigolactone receptor, followed by substrate hydrolysis and a conformational change from an inactive, or open state, to an active, or closed state. In the active state, the receptor associates with a signaling partner, MAX2. Recently, it was shown that this MAX2 association process acts as a strong contributor to the uniquely high signaling activity observed in ShHTL7; however, it is unknown why ShHTL7 has enhanced MAX2 association affinity. Using an umbrella sampling molecular dynamics approach, we characterized the association processes of AtD14, ShHTL7, a mutant of ShHTL7, and ShHTL6 with MAX2 homologue OsD3. From these results, we show that ShHTL7 has an enhanced standard binding free energy of OsD3 compared to those of the other receptors. Additionally, our results suggest that the overall topology of the T2/T3 helix region is likely an important modulator of MAX2 binding. Thus, differences in MAX2 association, modulated by differences in the T2/T3 helix region, are a contributor to differences in signaling activity between different strigolactone receptors.


Subject(s)
Carrier Proteins , Signal Transduction , Carrier Proteins/metabolism , Lactones/metabolism , Heterocyclic Compounds, 3-Ring/metabolism
9.
Plant Physiol Biochem ; 206: 108282, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38147706

ABSTRACT

Strigolactones, which are a group of plant hormones, have emerged as promising biomolecules for effectively managing oxidative stress in plants. Oxidative stress occurs when the production of reactive oxygen species (ROS) exceeds the plant's ability to detoxify or scavenge these harmful molecules. An elevation in reactive oxygen species (ROS) levels often occurs in response to a range of stressors in plants. These stressors encompass both biotic factors, such as fungal, viral, or nematode attacks, as well as abiotic challenges like intense light exposure, drought, salinity, and pathogenic assaults. This ROS surge can ultimately lead to cellular harm and damage. One of the key ways in which strigolactones help mitigate oxidative stress is by stimulating the synthesis and accumulation of antioxidants. These antioxidants act as scavengers of ROS, neutralizing their harmful effects. Additionally, strigolactones also regulate stomatal closure, which reduces water loss and helps alleviate oxidative stress during conditions of drought stress or water deficiencies. By understanding and harnessing the capabilities of strigolactones, it becomes possible to enhance crop productivity and enable plants to withstand environmental stresses in the face of a changing climate. This comprehensive review provides an in-depth exploration of the various roles of strigolactones in plant growth, development, and response to various stresses, with a specific emphasis on their involvement in managing oxidative stress. Strigolactones also play a critical role in detoxifying ROS while regulating the expression of genes related to antioxidant defense pathways, striking a balance between ROS detoxification and production.


Subject(s)
Heterocyclic Compounds, 3-Ring , Lactones , Oxidative Stress , Reactive Oxygen Species/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Antioxidants/metabolism , Plants/genetics , Stress, Physiological , Water/metabolism
10.
Int J Mol Sci ; 24(23)2023 Nov 26.
Article in English | MEDLINE | ID: mdl-38069097

ABSTRACT

Plants, the cornerstone of life on Earth, are constantly struggling with a number of challenges arising from both biotic and abiotic stressors. To overcome these adverse factors, plants have evolved complex defense mechanisms involving both a number of cell signaling pathways and a complex network of interactions with microorganisms. Among these interactions, the relationship between symbiotic arbuscular mycorrhizal fungi (AMF) and strigolactones (SLs) stands as an important interplay that has a significant impact on increased resistance to environmental stresses and improved nutrient uptake and the subsequent enhanced plant growth. AMF establishes mutualistic partnerships with plants by colonizing root systems, and offers a range of benefits, such as increased nutrient absorption, improved water uptake and increased resistance to both biotic and abiotic stresses. SLs play a fundamental role in shaping root architecture, promoting the growth of lateral roots and regulating plant defense responses. AMF can promote the production and release of SLs by plants, which in turn promote symbiotic interactions due to their role as signaling molecules with the ability to attract beneficial microbes. The complete knowledge of this synergy has the potential to develop applications to optimize agricultural practices, improve nutrient use efficiency and ultimately increase crop yields. This review explores the roles played by AMF and SLs in plant development and stress tolerance, highlighting their individual contributions and the synergistic nature of their interaction.


Subject(s)
Mycorrhizae , Mycorrhizae/physiology , Fungi/metabolism , Symbiosis , Lactones/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Plants/metabolism , Plant Roots/metabolism
11.
Plant Commun ; 4(6): 100675, 2023 Nov 13.
Article in English | MEDLINE | ID: mdl-37608548

ABSTRACT

Heat stress caused by global warming requires the development of thermotolerant crops to sustain yield. It is necessary to understand the molecular mechanisms that underlie heat tolerance in plants. Strigolactones (SLs) are a class of carotenoid-derived phytohormones that regulate plant development and responses to abiotic or biotic stresses. Although SL biosynthesis and signaling processes are well established, genes that directly regulate SL biosynthesis have rarely been reported. Here, we report that the MYB-like transcription factor AtMYBS1/AtMYBL, whose gene expression is repressed by heat stress, functions as a negative regulator of heat tolerance by directly inhibiting SL biosynthesis in Arabidopsis. Overexpression of AtMYBS1 led to heat hypersensitivity, whereas atmybs1 mutants displayed increased heat tolerance. Expression of MAX1, a critical enzyme in SL biosynthesis, was induced by heat stress and downregulated in AtMYBS1-overexpression (OE) plants but upregulated in atmybs1 mutants. Overexpression of MAX1 in the AtMYBS1-OE background reversed the heat hypersensitivity of AtMYBS1-OE plants. Loss of MAX1 function in the atmyb1 background reversed the heat-tolerant phenotypes of atmyb1 mutants. Yeast one-hybrid assays, chromatin immunoprecipitation‒qPCR, and transgenic analyses demonstrated that AtMYBS1 directly represses MAX1 expression through the MYB binding site in the MAX1 promoter in vivo. The atmybs1d14 double mutant, like d14 mutants, exhibited hypersensitivity to heat stress, indicating the necessary role of SL signaling in AtMYBS1-regulated heat tolerance. Our findings provide new insights into the regulatory network of SL biosynthesis, facilitating the breeding of heat-tolerant crops to improve crop production in a warming world.


Subject(s)
Arabidopsis , Thermotolerance , Arabidopsis/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Lactones/metabolism , Plants/metabolism , Thermotolerance/genetics
12.
J Sci Food Agric ; 103(8): 4234-4241, 2023 Jun.
Article in English | MEDLINE | ID: mdl-36732039

ABSTRACT

BACKGROUND: Monascus sp. has been used in fermented foods for centuries. It can synthesize yellow, red, and orange pigments as secondary metabolites. Here, we focused on yellow pigment monascin, responsible for anti-inflammation and antidiabetic effects, and investigated whether whey could be a suitable substrate with or without rice powder for monascin production using M. purpureus AHU 9085, M. pilosus NBRC 4520 and M. ruber NBRC 32318. RESULTS: The growth and monascin production of the three Monascus strains were dependent on three liquid media consisting of whey and/or rice. All strains showed the best growth in a rice and whey mixed medium, in which M. ruber NBRC 32318 exhibited the highest total monascin production. Subsequent investigation of the effects of whey components indicated that a mineral cocktail in whey was particularly effective in stimulating the monascin production efficiency of M. ruber NBRC 32318. However, this recipe exhibited less stimulation, or even inhibition, for M. pilosus NBRC 4520 and M. purpureus AHU 9085, respectively. In terms of total monascin production, rice with whey provided the highest amount due to growth promotion along with relatively high production efficiency. CONCLUSION: The effect of whey on growth and monascin production was strongly dependent on the Monascus strains. Even a mineral cocktail in whey could regulate monascin productivity in a strain-specific manner. Further studies are needed to elucidate the mechanism behind the diverse responses by the minerals in the production of monascin from Monascus. © 2023 Society of Chemical Industry.


Subject(s)
Monascus , Oryza , Monascus/metabolism , Whey/metabolism , Fermentation , Heterocyclic Compounds, 3-Ring/metabolism , Whey Proteins/metabolism , Oryza/metabolism , Pigments, Biological/metabolism
13.
Molecules ; 27(24)2022 Dec 19.
Article in English | MEDLINE | ID: mdl-36558190

ABSTRACT

There is increasing awareness of an association between the uptake of the HIV integrase inhibitor, dolutegravir, in first-line antiretroviral regimens with unusual weight gain and development of the metabolic syndrome, particularly in African women. Although seemingly unexplored, the development of systemic inflammation linked to the putative pro-inflammatory activity of dolutegravir represents a plausible pathophysiological mechanism of this unusual weight gain. This possibility was explored in the current study undertaken to investigate the effects of dolutegravir (2.5−20 µg/mL) on several pro-inflammatory activities of neutrophils isolated from the blood of healthy, adult humans. These activities included the generation of reactive oxygen species (ROS), degranulation (elastase release) and alterations in the concentrations of cytosolic Ca2+ using chemiluminescence, spectrophotometric and fluorimetric procedures, respectively. Exposure of neutrophils to dolutegravir alone resulted in the abrupt, dose-related, and significant (p < 0.0039−p < 0.0022) generation of ROS that was attenuated by the inclusion of the Ca2+-chelating agent, EGTA, or inhibitors of NADPH oxidase (diphenyleneiodonium chloride, DPI), phospholipase C (U733122), myeloperoxidase (sodium azide) and phosphoinositol-3-kinase (wortmannin). In addition, exposure to dolutegravir augmented the release of elastase by stimulus-activated neutrophils. These pro-inflammatory effects of dolutegravir on neutrophils were associated with significant, rapid, and sustained increases in the concentrations of cytosolic Ca2+ that appeared to originate from the extracellular compartment, seemingly consistent with an ionophore-like property of dolutegravir. These findings are preliminary and necessitate verification in the clinical setting of HIV infection. Nevertheless, given the complex link between inflammation and obesity, these pro-inflammatory interactions of dolutegravir with neutrophils may contribute to unexplained weight gain, possibly via the development of insulin resistance.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , Adult , Humans , Female , Reactive Oxygen Species/metabolism , HIV Infections/drug therapy , HIV Infections/metabolism , Neutrophils , Heterocyclic Compounds, 3-Ring/pharmacology , Heterocyclic Compounds, 3-Ring/metabolism , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Pancreatic Elastase/metabolism , Inflammation/chemically induced , Inflammation/drug therapy , Inflammation/metabolism
14.
PeerJ ; 10: e13551, 2022.
Article in English | MEDLINE | ID: mdl-35712547

ABSTRACT

Strigolactones (SLs) are a novel class of plant hormones that play critical roles in regulating various developmental processes and stress tolerance. Although the SL biosynthetic and signaling genes were already determined in some plants such as Arabidopsis and rice, the information of SL-related genes in grapevine (Vitis vinifera L.) remains largely unknown. In this study, the SL-related genes were identified from the whole grapevine genome, and their expression patterns under salt and drought stresses were determined. The results indicated that the five genes that involved in the SL biosynthesis included one each of the D27, CCD7, CCD8, MAX1 and LBO genes, as well as the three genes that involved in the SL signaling included one each of the D14, MAX2, D53 genes. Phylogenetic analysis suggested that these SL-related proteins are highly conserved among different plant species. Promoter analysis showed that the prevalence of a variety of cis-acting elements associated with hormones and abiotic stress existed in the promoter regions of these SL-related genes. Furthermore, the transcription expression analysis demonstrated that most SL-related genes are involved in the salt and drought stresses response in grapevine. These findings provided valuable information for further investigation and functional analysis of SL biosynthetic and signaling genes in response to salt and drought stresses in grapevine.


Subject(s)
Arabidopsis , Droughts , Phylogeny , Lactones/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Sodium Chloride/metabolism , Sodium Chloride, Dietary/metabolism , Arabidopsis/genetics
15.
J Chem Inf Model ; 62(7): 1712-1722, 2022 04 11.
Article in English | MEDLINE | ID: mdl-35192364

ABSTRACT

Parasitic weeds such as Striga have led to significant losses in agricultural productivity worldwide. These weeds use the plant hormone strigolactone as a germination stimulant. Strigolactone signaling involves substrate hydrolysis followed by a conformational change of the receptor to a "closed" or "active" state that associates with a signaling partner, MAX2/D3. Crystal structures of active and inactive AtD14 receptors have helped elucidate the structural changes involved in activation. However, the mechanism by which the receptor activates remains unknown. The ligand dependence of AtD14 activation has been disputed by mutagenesis studies showing that enzymatically inactive receptors are able to associate with MAX2 proteins. Furthermore, activation differences between strigolactone receptor in Striga, ShHTL7, and AtD14 could contribute to the high sensitivity to strigolactones exhibited by parasitic plants. Using molecular dynamics simulations, we demonstrate that both AtD14 and ShHTL7 could adopt an active conformation in the absence of ligand. However, ShHTL7 exhibits a higher population in the inactive apo state as compared to the AtD14 receptor. We demonstrate that this difference in inactive state population is caused by sequence differences between their D-loops and interactions with the catalytic histidine that prevent full binding pocket closure in ShHTL7. These results indicate that ligand hydrolysis would enhance the active state population by destabilizing the inactive state in ShHTL7 as compared to AtD14. We also show that the mechanism of activation is more concerted in AtD14 than in ShHTL7 and that the main barrier to activation in ShHTL7 is closing of the binding pocket.


Subject(s)
Striga , Carrier Proteins/metabolism , Heterocyclic Compounds, 3-Ring/chemistry , Heterocyclic Compounds, 3-Ring/metabolism , Lactones/chemistry , Lactones/metabolism , Lactones/pharmacology , Ligands , Plant Weeds/chemistry , Plant Weeds/metabolism , Striga/chemistry , Striga/metabolism
16.
BMC Plant Biol ; 22(1): 30, 2022 Jan 13.
Article in English | MEDLINE | ID: mdl-35027005

ABSTRACT

Strigolactone is a newly discovered type of plant hormone that has multiple roles in modulating plant responses to abiotic stress. Herein, we aimed to investigate the effects of exogenous GR24 (a synthetic analogue of strigolactone) on plant growth, photosynthetic characteristics, carbohydrate levels, endogenous strigolactone content and antioxidant metabolism in cucumber seedlings under low light stress. The results showed that the application of 10 µM GR24 can increase the photosynthetic efficiency and plant biomass of low light-stressed cucumber seedlings. GR24 increased the accumulation of carbohydrates and the synthesis of sucrose-related enzyme activities, enhanced antioxidant enzyme activities and antioxidant substance contents, and reduced the levels of H2O2 and MDA in cucumber seedlings under low light stress. These results indicate that exogenous GR24 might alleviate low light stress-induced growth inhibition by regulating the assimilation of carbon and antioxidants and endogenous strigolactone contents, thereby enhancing the tolerance of cucumber seedlings to low light stress.


Subject(s)
Adaptation, Ocular/drug effects , Cucumis sativus/drug effects , Cucumis sativus/growth & development , Cucumis sativus/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Lactones/metabolism , Crops, Agricultural/drug effects , Crops, Agricultural/growth & development , Crops, Agricultural/metabolism
17.
Plant Physiol ; 188(1): 97-110, 2022 01 20.
Article in English | MEDLINE | ID: mdl-34718781

ABSTRACT

Strigolactones (SLs) are a class of plant hormones that mediate biotic interactions and modulate developmental programs in response to endogenous and exogenous stimuli. However, a comprehensive view on the spatio-temporal pattern of SL signaling has not been established, and tools for a systematic in planta analysis do not exist. Here, we present Strigo-D2, a genetically encoded ratiometric SL signaling sensor that enables the examination of SL signaling distribution at cellular resolution and is capable of rapid response to altered SL levels in intact Arabidopsis (Arabidopsis thaliana) plants. By monitoring the abundance of a truncated and fluorescently labeled SUPPRESSOR OF MAX2 1-LIKE 6 (SMXL6) protein, a proteolytic target of the SL signaling machinery, we show that all cell types investigated have the capacity to respond to changes in SL levels but with very different dynamics. In particular, SL signaling is pronounced in vascular cells but low in guard cells and the meristematic region of the root. We also show that other hormones leave Strigo-D2 activity unchanged, indicating that initial SL signaling steps work in isolation from other hormonal signaling pathways. The specificity and spatio-temporal resolution of Strigo-D2 underline the value of the sensor for monitoring SL signaling in a broad range of biological contexts with highly instructive analytical depth.


Subject(s)
Arabidopsis/growth & development , Arabidopsis/genetics , Arabidopsis/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Lactones/metabolism , Meristem/metabolism , Plant Growth Regulators/metabolism , Signal Transduction/drug effects , Gene Expression Regulation, Plant , Genes, Plant , Meristem/genetics , Meristem/growth & development , Plant Growth Regulators/genetics , Signal Transduction/genetics
18.
Plant Cell Environ ; 45(2): 512-527, 2022 02.
Article in English | MEDLINE | ID: mdl-34719040

ABSTRACT

Nitrogen (N) and phosphorus (P) are among the most important macronutrients for plant growth and development, and the most widely used as fertilizers. Understanding how plants sense and respond to N and P deficiency is essential to optimize and reduce the use of chemical fertilizers. Strigolactones (SLs) are phytohormones acting as modulators and sensors of plant responses to P deficiency. In the present work, we assess the potential role of SLs in N starvation and in the N-P signalling interplay. Physiological, transcriptional and metabolic responses were analysed in wild-type and SL-deficient tomato plants grown under different P and N regimes, and in plants treated with a short-term pulse of the synthetic SL analogue 2'-epi-GR24. The results evidence that plants prioritize N over P status by affecting SL biosynthesis. We also show that SLs modulate the expression of key regulatory genes of phosphate and nitrate signalling pathways, including the N-P integrators PHO2 and NIGT1/HHO. The results support a key role for SLs as sensors during early plant responses to both N and phosphate starvation and mediating the N-P signalling interplay, indicating that SLs are involved in more physiological processes than so far proposed.


Subject(s)
Heterocyclic Compounds, 3-Ring/metabolism , Lactones/metabolism , Nitrogen/physiology , Phosphorus/physiology , Signal Transduction , Solanum lycopersicum/physiology
19.
Plant Physiol ; 188(1): 255-267, 2022 01 20.
Article in English | MEDLINE | ID: mdl-34687296

ABSTRACT

During secondary growth, meristematic cells in the cambium can either proliferate to maintain the stem cell population or differentiate into xylem or phloem. The balance between these two developmental trajectories is tightly regulated by many environmental and endogenous cues. Strigolactones (SLs), a class of plant hormones, were previously reported to regulate secondary growth by promoting cambium activity. However, the underlying molecular mechanisms of SL action in plant secondary growth are not well understood. We performed histological, genetic, and biochemical analyses using genetic materials in Arabidopsis (Arabidopsis thaliana) with altered activity of the transcription factors BRI1-EMS-SUPPRESSOR1 (BES1) or WUSCHEL-related HOMEOBOX4 (WOX4) or lacking MORE AXILLARY SHOOT2 (MAX2), a key positive component in the SL signaling pathway. We found that BES1, a downstream regulator in the SL signaling pathway that promotes shoot branching and xylem differentiation, also inhibits WOX4 expression, a key regulator of cambium cell division in the intercellular TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF)-TDIF RECEPTOR (TDR) signaling pathway. The antagonistic roles of BES1 and WOX4 in the regulation of cambium activity may integrate intercellular TDIF signals to efficiently and bidirectionally modulate cambium cell proliferation and differentiation. As both BES1 and WOX4 are widely involved in various endogenous signals and responses to environmental stimuli, these findings may provide insight into the dynamic regulation of cambium development.


Subject(s)
Arabidopsis/genetics , Arabidopsis/metabolism , Cambium/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Homeodomain Proteins/metabolism , Lactones/metabolism , Signal Transduction/drug effects , Transcription Factors , Cambium/genetics , Gene Expression Regulation, Plant , Genes, Plant , Genetic Variation , Genotype , Homeodomain Proteins/genetics
20.
Int J Mol Sci ; 22(24)2021 Dec 20.
Article in English | MEDLINE | ID: mdl-34948474

ABSTRACT

Belowground interactions of plants with other organisms in the rhizosphere rely on extensive small-molecule communication. Chemical signals released from host plant roots ensure the development of beneficial arbuscular mycorrhizal (AM) fungi which in turn modulate host plant growth and stress tolerance. However, parasitic plants have adopted the capacity to sense the same signaling molecules and to trigger their own seed germination in the immediate vicinity of host roots. The contribution of AM fungi and parasitic plants to the regulation of phytohormone levels in host plant roots and root exudates remains largely obscure. Here, we studied the hormonome in the model system comprising tobacco as a host plant, Phelipanche spp. as a holoparasitic plant, and the AM fungus Rhizophagus irregularis. Co-cultivation of tobacco with broomrape and AM fungi alone or in combination led to characteristic changes in the levels of endogenous and exuded abscisic acid, indole-3-acetic acid, cytokinins, salicylic acid, and orobanchol-type strigolactones. The hormonal content in exudates of broomrape-infested mycorrhizal roots resembled that in exudates of infested non-mycorrhizal roots and differed from that observed in exudates of non-infested mycorrhizal roots. Moreover, we observed a significant reduction in AM colonization of infested tobacco plants, pointing to a dominant role of the holoparasite within the tripartite system.


Subject(s)
Fungi/physiology , Mycorrhizae/physiology , Nicotiana/growth & development , Orobanche/growth & development , Abscisic Acid/metabolism , Chromatography, Liquid , Cytokinins/metabolism , Heterocyclic Compounds, 3-Ring/metabolism , Host-Pathogen Interactions , Indoleacetic Acids/metabolism , Lactones/metabolism , Mass Spectrometry , Orobanche/microbiology , Plant Roots/metabolism , Plant Roots/microbiology , Salicylic Acid/metabolism , Nicotiana/microbiology
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