Building of CuO2@Cu-TA@DSF/DHA Nanoparticle Targets MAPK Pathway to Achieve Synergetic Chemotherapy and Chemodynamic for Pancreatic Cancer Cells DOI Creative Commons
Jiaru Zhang,

Zuoping Li,

Zhenzhen Xie

и другие.

Pharmaceutics, Год журнала: 2024, Номер 16(12), С. 1614 - 1614

Опубликована: Дек. 19, 2024

Background/Objectives: With the increase of reactive oxygen species (ROS) production, cancer cells can avoid cell death and damage by up-regulating antioxidant programs. Therefore, it will be more effective to induce using targeted strategies further improve ROS levels drugs that inhibit Methods: Considering dihydroartemisinin (DHA) cause oxidative protein, DNA, or lipids producing excessive ROS, while, disulfiram (DSF) glutathione (GSH) achieve therapeutic effect inhibiting system amplifying stress, they were co-loaded onto copper peroxide nanoparticles (CuO2) coated with tannic acid (Cu-TA), build a drug delivery CuO2@Cu-TA@DSF/DHA (CCTDD NPs). In response tumor microenvironment, DHA interacts ion (Cu2+) produce double (diethylthiocarbamate)-copper (II) (CuET) is generated complexation DSF Cu2+, which consumes GSH inhibits system. Meanwhile, utilizing Fenton-like induced multi-copper mode storm, activate MAPK pathway, chemotherapy (CT) chemodynamic (CDT). Results: Taking pancreatic lines PANC-1 BxPC-3 as research objects, line experiments in vitro proved CCTDD NPs exhibit efficient cytotoxicity on cells. Conclusions: The show great potential resisting provides simple strategy for designing powerful metal matrix composites.

Язык: Английский

NLR signaling in plants: from resistosomes to second messengers DOI Creative Commons
Shijia Huang, Aolin Jia, Ma ShouCai

и другие.

Trends in Biochemical Sciences, Год журнала: 2023, Номер 48(9), С. 776 - 787

Опубликована: Июнь 30, 2023

Pathogen effector-induced assembly of resistosomes has been established as an important event for nucleotide binding and leucine-rich repeat-containing receptor (NLR) signaling in plants.The pentameric coiled-coil domain-containing NLR (CNL) act Ca2+-permeable channels, whereas the tetrameric Toll-interleukin 1-like (TIR) (TNL) are NADase holoenzymes.TNL catalyze production nucleotide-derived second messengers to activate downstream helper NLRs activated disease resistance 1 (ADR1) N requirement gene (NRG1) CNL class. Thus, CNLs TNLs converge on Ca2+ signals trigger plant immunity.NLR cross-talks with pattern-triggered immunity (PTI) pathways.NLR pathways plants negatively regulated by both hosts pathogens. Nucleotide receptors (NLRs) have a critical role through direct or indirect recognition pathogen effectors. Recent studies demonstrated that such induces formation large protein complexes called mediate immune signaling. Some influx acting others function active NADases messengers. In this review we summarize these resistosome-mediated derivatives. We also discuss events regulation resistosome Plants rely multiple detect invading microbial pathogens mount responses [1.Ngou B.P.M. et al.Thirty years resistance: zig-zag system.Plant Cell. 2022; 34: 1447-1478Crossref PubMed Scopus (45) Google Scholar,2.Zhou J.M. Zhang Y. Plant immunity: danger perception signaling.Cell. 2020; 181: 978-989Abstract Full Text PDF (328) Scholar]. One subfamily pattern-recognition (PRRs) (see Glossary) at cell surface Scholar, 2.Zhou 3.DeFalco T.A. Zipfel C. Molecular mechanisms early signaling.Mol. 2021; 81: 3449-3467Abstract (0) PRRs recognize pathogen-associated molecular patterns (PAMPs) host-derived damage-associated (DAMPs), leading (PTI). PTI constitutes first line inducible defense against can breach layer secreting effector proteins into cells dampen PTI. To counteract virulence activity effectors, evolved receptors: intracellular NLRs. specifically proteins, inducing effector-triggered (ETI) confer race-specific site entry Scholar,4.Jones J.D.G. al.Intracellular innate surveillance devices animals.Science. 2016; 354aaf6395Crossref different structures subcellular localizations but conserved responses, including influx, bursts reactive oxygen species (ROS), phytocytokines phytohormones, transcriptional reprogramming Probably reason, ETI tightly connected [5.Yuan M. al.Pattern-recognition required NLR-mediated immunity.Nature. 592: 105-109Crossref (351) Scholar,6.Ngou al.Mutual potentiation cell-surface receptors.Nature. 110-115Crossref (329) However, differ timing, amplitude, duration defense, which could be determining their physiological outcomes. addition includes hypersensitive response (HR), form rapid localized programmed death infection [7.Jones J.D. Dangl J.L. The system.Nature. 2006; 444: 323-329Crossref (8693) largest hundreds distinct members [4.Jones two domains: central nucleotide-binding oligomerization domain (NOD), C-terminal repeat (LRR) domain. A variable (CC) is attached terminus, resulting TIR-NLR CC-NLR (CNL), respectively [8.Maruta N. al.Structural basis activation signalling plants.Immunogenetics. 74: 5-26Crossref (25) Scholar,9.Hu Z. Chai J. Assembly architecture inflammasomes.Annu. Rev. Biophys. 52: 8.1-8.22Google pathogen-sensing NLRs, there some (h) translate from [10.Feehan al.Plant get little help friends.Curr. Opin. Biol. 56: 99-108Crossref (18) Scholar,11.Jubic L.M. al.Help wanted: responses.Curr. 2019; 50: 82-94Crossref (139) Examples hNLRs include Resistance Powdery Mildew 8 (RPW8) family [12.Wu al.Differential TNL-mediated redundant CNLs.New Phytol. 222: 938-953Crossref (118) 13.Castel B. al.Diverse defence via RPW8-NLR NRG1.New 966-980Crossref (144) 14.Qi T. al.NRG1 functions EDS1 regulate TIR-NLR-mediated Nicotiana benthamiana.Proc. Natl. Acad. Sci. U. S. A. 2018; 115: E10979-E10987Crossref (121) 15.Collier S.M. al.Cell mediated N-terminal domains unique highly class NB-LRR protein.Mol. Microbe Interact. 2011; 24: 918-931Crossref (230) Scholar] (Figure 1) (NRCs) [16.Adachi H. Kamoun networks plants.Essays Biochem. 66: 541-549Crossref (4) Scholar,17.Wu C.H. al.NLR network mediates diverse pathogens.Proc. 2017; 114: 8113-8118Crossref (211) More recent signaling, many sensor Solanaceae, depends NRCs upon [18.Ahn H.K. al.Effector-dependent NRC Rpi-amr3 Rpi-amr1.EMBO 2023; 42e111484Crossref (5) Scholar,19.Contreras M.P. al.Sensor helpers pathogens.EMBO 42e111519PubMed messengers, calcium ion derivations. crosstalk between negative effectors host regulators. directly indirectly. For example, interaction benthamiana TNL Roq1 (recognition XopQ its recognized (Xanthomonas outer Q) [20.Schultink al.Roq1 Xanthomonas Pseudomonas HopQ1.Plant 92: 787-795Crossref (82) Scholar,21.Martin R. al.Structure ROQ1 recognizing XopQ.Science. 370eabd9993Crossref (174) Scholar], arabidopsis RPP1 Peronospora parasitica ATR1 (Arabidopsis thaliana [22.Ma al.Direct pathogen-induced complex holoenzyme.Science. 370abe3069Crossref (169) Scholar,23.Krasileva K.V. al.Activation Arabidopsis specified planta association cognate oomycete effector.Plant 2010; 22: 2444-2458Crossref (220) wheat Sr35 (stem rust 35) AvrSr35 [24.Zhao Y.-B. al.Pathogen triggers mechanism.Sci. Adv. 8eabq5108Crossref (13) 25.Forderer al.A defines common principles channels.Nature. 610: 532-539Crossref 26.Salcedo al.Variation determines stem race Ug99.Science. 358: 1604-1606Crossref (117) spp, Hyaloperonospora parasitica, Puccinia graminis tritici, respectively. monitoring effector-mediated perturbations targets. example ZAR1 (HOPZ-ACTIVATED RESISTANCE [27.Lewis al.Allele-specific attenuation syringae HopZ1a type III protein.PLoS Genet. 6e1000894Crossref (111) exists preformed kinase RKS1 (resistance-related normal conditions recognizes AvrAC indirectly uridylylation another PBL2 (PBS1-like 2) [28.Wang al.Ligand-triggered allosteric ADP release primes complex.Science. 364aav5868Crossref (231) Scholar,29.Wang G. al.The decoy substrate pseudokinase specify modified-self plants.Cell Host Microbe. 2015; 18: 285-295Abstract (156) Scholar]; AvrAC-uridylylated associates consequently activates ZAR1-mediated immunity. Alternatively, cases, may not necessarily CHS3 (CHILLING SENSITIVE 3)/CSA1 (CONSTITUTIVE SHADE-AVOIDANCE pair detects PRR coreceptor BAK1 (BRASSINOSTEROID INSENSITIVE 1-associated [30.Yang al.Allelic variation CHS3/CSA1 reveals functional cell-death regulatory modes.Cell 30: 1701-1716Abstract (7) malectin-like receptor-like LET1 autoimmunity SUMM2 (SUPPRESSOR OF MKK1 MKK2) MEKK2 (MAP/ERK kinase-2) scaffolding [31.Liu LETUM1 modulates scaffolding.Nat. Plants. 6: 1106-1115Crossref (26) Effector leads termed 1). Cryoelectron microscopy (cryoEM) analyses show containing ZAR1, RKS1, uridylylated (PBL2UMP) forms wheel-like [32.Wang al.Reconstitution structure conferring immunity.Science. 364aav5870Crossref (368) 1, left). Pentamerization mainly NOD module PBL2UMP being presented rim wheel 2). contrast AvrSr35, remarkably similar Scholar,25.Forderer more study showed oligomeric NRG1 likely formed plasma membrane (PM) [33.Feehan al.Oligomerization requires activation.Proc. 120e2210406120Crossref (3) Interestingly, resistosomes, underlying await further elucidation By comparison, end results right). induced [21.Martin As seen primarily Structural modeling sequestered inactive Scholar,24.Zhao Scholar,32.Wang suggesting oligomerization. it remains unknown whether all resistosomes. Many pairs, executor initiating [34.Xi al.Insight mode action paired receptors.Essays 513-526Crossref (2) Whether how represent challenge understanding mechanisms. cryoEM resistosome, five α1-helices solvent-exposed shaped like channel pore Functional data support ETI. Importantly, electrophysiological evidence supports [35.Bi calcium-permeable triggering 184: 3528-3541Abstract (181) bottom Single molecule imaging hours before loss PM integrity These suggest acts α1 distantly related [36.Adachi al.An motif functionally across species.eLife. 8e49956Crossref (92) Ca2+-channel among Indeed, bears [25.Forderer essential helix well-defined resistosome. It environment funnel-shaped localization shown RPM1 (resistance pv. maculicola [37.El Kasmi F. al.Signaling plasma-membrane self-association full-length protein.Proc. E7385-E7394Crossref (70) RPS2 P. [38.Axtell M.J. Staskawicz B.J. Initiation RPS2-specified coupled AvrRpt2-directed elimination RIN4.Cell. 2003; 112: 369-377Abstract (643) bethamiana Tm-22 [39.Wang NB-ARC domain-mediated CC domain.PLoS Pathog. 16e1008475Crossref (20) ZAR1-like examined. TNL-activated hNLRs, NRG1s, ADR1s display autoactive Scholar,40.Jacob "helper" nonselective cation channels.Science. 373: 420-425Crossref (125) indicating Solanaceae (SD) found noncanonical [41.Seong K. al.Evolution genes wild tomato species.New 227: 1530-1543Crossref (36) themselves structures. undetermined activity. Multiple lines extracellular [42.Xu tale families: channels immunity.Plant 1551-1567Crossref (19) Scholar,43.Kim N.H. al.Con-Ca2+-tenating channels.New 234: 813-818Crossref (8) Elevation concentrations one earliest during Gain-of-function mutations CNGC19/20 (CYCLIC NUCLEOTIDE GATED CHANNEL19/20) increased constitutively (enhanced susceptibility 1)- SA (salicylic acid)-dependent [44.Yu X. kinases BAK1/SERK4 channel-mediated cellular homeostasis containment.Curr. 29: 3778-3790Abstract (64) Scholar,45.Zhao mis-regulated cyclic nucleotide-gated cytosolic elevation Arabidopsis.New 230: 1078-1094Crossref (33) Unregulated Sr35, NRG1, ADR1 sufficient recapitulate CNL-mediated eukaryotic Although released internal pools contribute pharmacological blocking compartments ruthenium red (RR) less efficient inhibition HR than blocker LaCl3 [46.Gao heat-activated 6 involved heat shock responses.Plant 2012; 70: 1056-1069Crossref supporting notion major responses. Nuclear [47.Ludke D. yet? Nucleocytoplasmic coordination immunity.New 236: 24-42Crossref mechanism associated enigmatic. Several interact factors [48.Wang al.Diversity, receptors.J. Integr. 63: 283-296Crossref (11) programming nucleus. transcription set genes, other reprogramming. NRG1A PM- nucleus-localized activation, only PM-resident oligomers oligomerization-independent function. Increases nuclear free reported various stresses [49.Pauly nucleus together cytosol generates specific signatures tobacco suspension culture cells.Cell Calcium. 2001; 413-421Crossref 50.van Der Luit A.H. al.Distinct calmodulin expression tobacco.Plant Physiol. 1999; 121: 705-714Crossref 51.Xiong T.C. al.Isolated nuclei mechanical thermal sensors signalling.Plant 2004; 40: 12-21Crossref should kept mind spatial distribution uniform, steep gradients few nanometers away [52.Pangršič al.EF-hand buffers exocytosis sensory hair cells.Proc. E1028-E1037Crossref transported PM-localized and/or reach possible continuum organelle endoplasmic reticulum (ER). Such result An CNGC15 symbiotic oscillation [53.Charpentier al.Nuclear-localized oscillations.Science. 352: 1102-1105Crossref While signals, they TNLs, CNLs, NADases. ATR1-induced significantly enhances activity, holoenzyme enzymatic encoded TIR [54.Wan L. al.TIR NAD+-cleaving enzymes promote death.Science. 365: 799-803Crossref (226) Scholar,55.Horsefield al.NAD+ cleavage animal pathways.Science. 793-799Crossref (244) TIR-only bacterial HopBA1 (RBA1) [56.Nishimura M.T. al.TIR-only RBA1 Arabidopsis.Proc. E2053-E2062Crossref (93) Tetramerization composite sites Scholar,22.Ma [57.Shi SARM1 recognition, small molecules.Mol. 82: 1643-1659Abstract (27) 58.Manik M.K. al.Cyclic ribose isomers: production, chemical structures, signaling.Science. 377eadc8969Crossref 59.Hogrel nucleotide-induced helical effector.Nature. 608: 808-812Crossref analogs PAD4 (phytoalexin deficient 4)

Язык: Английский

Процитировано

45

Pathogen perception and signaling in plant immunity DOI Creative Commons
Peter N. Dodds, Jian Chen, Megan A. Outram

и другие.

The Plant Cell, Год журнала: 2024, Номер 36(5), С. 1465 - 1481

Опубликована: Янв. 23, 2024

Abstract Plant diseases are a constant and serious threat to agriculture ecological biodiversity. Plants possess sophisticated innate immunity system capable of detecting responding pathogen infection prevent disease. Our understanding this has grown enormously over the past century. Early genetic descriptions plant disease resistance virulence were embodied in gene-for-gene hypothesis, while physiological studies identified pathogen-derived elicitors that could trigger defense responses cells tissues. Molecular these phenomena have now coalesced into an integrated model involving cell surface intracellular detection specific molecules proteins culminating induction various cellular responses. Extracellular receptors engage distinct signaling processes but converge on many similar outputs with substantial evidence for integration pathways interdependent networks controlling outcomes. Many molecular details recognition known, providing opportunities bioengineering enhance protection from Here we provide overview current main principles immunity, emphasis key scientific milestones leading insights.

Язык: Английский

Процитировано

33

Plant NLR immunity activation and execution: a biochemical perspective DOI Creative Commons
Federica Locci, Jane E. Parker

Open Biology, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 1, 2024

Plants deploy cell-surface and intracellular receptors to detect pathogen attack trigger innate immune responses. Inside host cells, families of nucleotide-binding/leucine-rich repeat (NLR) proteins serve as sensors or downstream mediators defence outputs cell death, which prevent disease. Established genetic underpinnings NLR-mediated immunity revealed various strategies plants adopt combat rapidly evolving microbial pathogens. The molecular mechanisms NLR activation signal transmission components controlling execution were less clear. Here, we review recent protein structural biochemical insights plant sensor signalling functions. When put together, the data show how different families, whether transducers, converge on nucleotide-based second messengers cellular calcium confer immunity. Although pathogen-activated NLRs in engage plant-specific machineries promote defence, comparisons with mammalian receptor counterparts highlight some shared working principles for across kingdoms.

Язык: Английский

Процитировано

20

Activation and inhibition mechanisms of a plant helper NLR DOI

Yinyan Xiao,

Xiaoxian Wu,

Zaiqing Wang

и другие.

Nature, Год журнала: 2025, Номер unknown

Опубликована: Фев. 12, 2025

Язык: Английский

Процитировано

2

Structure, biochemical function, and signaling mechanism of plant NLRs DOI Creative Commons
Jizong Wang, Wen Song, Jijie Chai

и другие.

Molecular Plant, Год журнала: 2022, Номер 16(1), С. 75 - 95

Опубликована: Ноя. 22, 2022

To counter pathogen invasion, plants have evolved a large number of immune receptors, including membrane-resident pattern recognition receptors (PRRs) and intracellular nucleotide-binding leucine-rich repeat (NLRs). Our knowledge about PRR NLR signaling mechanisms has expanded significantly over the past few years. Plant NLRs form multi-protein complexes called resistosomes in response to effectors, mediated by converges on Ca2+-permeable channels. channels important for also been identified. These findings highlight crucial role Ca2+ triggering plant signaling. In this review, we first discuss structural biochemical non-canonical then summarize our immune-related their roles We potential intricate interaction between

Язык: Английский

Процитировано

52

Plasma membrane association and resistosome formation of plant helper immune receptors DOI Creative Commons

Zaiqing Wang,

Xiaoxiao Liu, Jie Yu

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(32)

Опубликована: Июль 31, 2023

Intracellular plant immune receptors, termed NLRs (Nucleotide-binding Leucine-rich repeat Receptors), confer effector-triggered immunity. Sensor are responsible for pathogen effector recognition. Helper function downstream of sensor to transduce signaling and induce cell death Activation that contain TIR (Toll/interleukin-1receptor) domains generates small molecules an association between a heterodimer signalosome EDS1 (EnhancedDisease Susceptibility 1)/SAG101 (Senescence-AssociatedGene 101) the helper NLR NRG1 (NRequired Gene 1). Autoactive NRG1s oligomerize form calcium channels largely localized at plasma membrane (PM). The molecular mechanisms PM effector-induced oligomerization not well characterized. We demonstrate require positively charged residues in their N-terminal phospholipid binding before after activation, despite conformational changes accompany activation. activation TIR-containing induces cytoplasmic pool EDS1/SAG101 is critical function. cannot be detected oligomerized resistosome, suggesting additional unknown triggers might required dissociation from previously described NRG1/EDS1/SAG101 heterotrimer subsequent oligomerization. Alternatively, resulting abrogate interface association. Our data provide observations regarding dynamic during underpin updated model resistosome formation.

Язык: Английский

Процитировано

33

Calcium homeostasis and signaling in plant immunity DOI Creative Commons
Chao Wang, Sheng Luan

Current Opinion in Plant Biology, Год журнала: 2023, Номер 77, С. 102485 - 102485

Опубликована: Дек. 2, 2023

Calcium (Ca2+) signaling consists of three steps: (1) initiation a change in cellular Ca2+ concentration response to stimulus, (2) recognition the through direct binding by its sensors, (3) transduction signal elicit downstream responses. Recent studies have uncovered central role for both layers immune responses initiated plasma membrane (PM) and intracellular receptors, respectively. These advances our understanding are attributed several lines research, including invention genetically-encoded reporters recording signals, identification channels their gating mechanisms, functional analysis proteins (Ca2+ sensors). This review analyzes recent literature that illustrates importance homeostasis plant innate immunity, featuring intricate Ca2+dependent positive negative regulations.

Язык: Английский

Процитировано

33

New Biochemical Principles for NLR Immunity in Plants DOI Creative Commons
Jijie Chai, Wen Song, Jane E. Parker

и другие.

Molecular Plant-Microbe Interactions, Год журнала: 2023, Номер 36(8), С. 468 - 475

Опубликована: Авг. 1, 2023

While working for the United States Department of Agriculture on North Dakota Agricultural College campus in Fargo, Dakota, 1940s and 1950s, Harold H. Flor formulated genetic principles coevolving plant host-pathogen interactions that govern disease resistance or susceptibility. His ‘gene-for-gene’ legacy runs deep modern pathology continues to inform molecular models immune recognition signaling. In this review, we discuss recent biochemical insights immunity conferred by nucleotide-binding domain/leucine-rich-repeat (NLR) receptors, which are major gene-for-gene determinants nature cultivated crops. Structural analyses pathogen-activated NLR oligomers (resistosomes) reveal how different subtypes converge various ways calcium (Ca 2+ ) signaling promote pathogen host cell death. Especially striking is identification nucleotide-based signals generated enzymatically toll-interleukin 1 receptor (TIR) domain NLRs. These small molecules part an emerging family TIR-produced cyclic noncyclic nucleotide steer cell-death responses bacteria, mammals, plants. A combined genetic, molecular, understanding activation provides exciting new opportunities combatting diseases [Formula: see text] Copyright © 2023 The Author(s). This open access article distributed under CC BY-NC-ND 4.0 International license .

Язык: Английский

Процитировано

26

Immune signaling: receptor-like proteins make the difference DOI

Wen R.H. Huang,

M.H.A.J. Joosten

Trends in Plant Science, Год журнала: 2024, Номер unknown

Опубликована: Апрель 1, 2024

Язык: Английский

Процитировано

13

Plant cell surface immune receptors—Novel insights into function and evolution DOI
Lisha Zhang,

Chenlei Hua,

Denis Janocha

и другие.

Current Opinion in Plant Biology, Год журнала: 2023, Номер 74, С. 102384 - 102384

Опубликована: Июнь 3, 2023

Язык: Английский

Процитировано

21