Manipulation Of Reactive Oxygen Species Research Articles

Functionality of Reactive Oxygen Species (ROS) in Plants: Toxicity and Control in Poaceae Crops Exposed to Abiotic Stress.

Agriculture and changing environmental conditions are closely related, as weather changes could adversely affect living organisms or regions of crop cultivation. Changing environmental conditions trigger different abiotic stresses, which ultimately cause the accumulation of reactive oxygen species (ROS) in plants. Common ROS production sites are the chloroplast, endoplasmic reticulum, plasma membrane, mitochondria, peroxisomes, etc. The imbalance in ROS production and ROS detoxification in plant cells leads to oxidative damage to biomolecules such as lipids, nucleic acids, and proteins. At low concentrations, ROS initiates signaling events related to development and adaptations to abiotic stress in plants by inducing signal transduction pathways. In plants, a stress signal is perceived by various receptors that induce a signal transduction pathway that activates numerous signaling networks, which disrupt gene expression, impair the diversity of kinase/phosphatase signaling cascades that manage the stress response in the plant, and result in changes in physiological responses under various stresses. ROS production also regulates ABA-dependent and ABA-independent pathways to mitigate drought stress. This review focuses on the common subcellular location of manufacturing, complex signaling mechanisms, and networks of ROS, with an emphasis on cellular effects and enzymatic and non-enzymatic antioxidant scavenging mechanisms of ROS in Poaceae crops against drought stress and how the manipulation of ROS regulates stress tolerance in plants. Understanding ROS systems in plants could help to create innovative strategies to evolve paths of cell protection against the negative effects of excessive ROS in attempts to improve crop productivity in adverse environments.

Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene

AbstractInvestigations into the selective oxidation of inert sp3 C−H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure‐activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene‐based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor‐acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG‐579 using a photocatalytic protocol.

Triazine Frameworks for the Photocatalytic Selective Oxidation of Toluene.

Investigations into the selective oxidation of inert sp3 C-H bonds using polymer photocatalysts under mild conditions have been limited. Additionally, the structure-activity relationship of photocatalysts often remains insufficiently explored. Here, a series of thiophene-based covalent triazine frameworks (CTFs) are used for the efficient and selective oxidation of hydrocarbons to aldehydes or ketones under ambient aerobic conditions. Spectroscopic methods conducted in situ and density functional theory (DFT) calculations revealed that the sulfur atoms within the thiophene units play a pivotal role as oxidation sites due to the generation of photogenerated holes. The effect of photogenerated holes on photocatalytic toluene oxidation was investigated by varying the length of the spacer in a CTF donor-acceptor based photocatalyst. Furthermore, the manipulation of reactive oxygen species was employed to enhance selectivity by weakening the peroxidative capacity. As an illustrative example, this study successfully demonstrated the synthesis of a precursor of the neurological drug AMG-579 using a photocatalytic protocol.

Dissecting the pleiotropic roles of reactive oxygen species (ROS) in lung cancer: From carcinogenesis towardtherapy.

Lung cancer is a major cause of morbidity and mortality. The specific pulmonary structure to directly connect with ambient air makes it more susceptible to damage from airborne toxins. External oxidative stimuli and endogenous reactive oxygen species (ROS) play a crucial role in promoting lung carcinogenesis and development. The biological properties of higher ROS levels in tumor cells than in normal cells make them more sensitive and vulnerable to ROS injury. Therefore, the strategy of targeting ROS has been proposed for cancer therapy for decades. However, it is embarrassing that countless attempts at ROS-based therapies have had very limited success, and no FDA approval in the anticancer list was mechanistically based on ROS manipulation. Even compared with the untargetable proteins, such as transcription factors, ROS are more difficult to be targeted due to their chemical properties. Thus, the pleiotropic roles of ROS provide therapeutic potential for anticancer drug discovery, while a better dissection of the mechanistic action and signaling pathways is a prerequisite for future breakthroughs. This review discusses the critical roles of ROS in cancer carcinogenesis, ROS-inspired signaling pathways, and ROS-based treatment, exemplified by lung cancer. In particular, an eight considerations rule is proposed for ROS-targeting strategies and drug design and development.

Achieving precise non-invasive ROS spatiotemporal manipulation for colon cancer immunotherapy

Colon cancer (CC) stands as a formidable global health challenge, ranking as the third leading cause of cancer-related mortality. Traditional photodynamic therapy encounters limitations stemming from the limited penetration depth of light and the effective regulation of reactive oxygen species (ROS). Here, we present an in-situ ROS spatiotemporal manipulation system that synergizes the power of piezoelectric nanoparticles with potent immune adjuvants. This exclusive ROS nanogenerator exhibits precision in targeting colon tumor sites, inducing controlled oxidative stress to eliminate malignant cells, while simultaneously unleashing the full potential of the immune system to suppress cancer cell growth and impede metastasis. Notably, this system achieves spatiotemporal manipulation of ROS through piezocatalytic mechanisms triggered self-generated ROS. Moreover, it skillfully customizes ROS production in response to tumor size, optimizing therapeutic efficacy with precision. To enhance the therapeutic efficacy, glucan, a bioactive polysaccharide that augments the immune response while simultaneously inhibiting the spread of cancer cells, is integrated. This cancer treatment approach is enabling precise ROS generation and immune modulation at the tumor site, ushering in a new era of dynamic immunotherapy.

Highly efficient photo-driven generation and elimination of reactive oxygen species in biological environment by gold nanoclusters

Reactive oxygen species (ROS) play an essential role in cell signalling, pathogen defence, and maintaining cellular homeostasis. The photocatalysts are highly desired in the photo-driven in-situ ROS generation and elimination in biological environment. Here, we present the highly efficient photo-driven generation and elimination of ROS in biological environment by glutathione (GSH)-protected gold nanoclusters (AuNCs). In extracellular environment, AuNCs can generate hydrogen peroxide (H2O2) through a two-electron oxygen reduction reaction (ORR) without any additional sacrifices. On the other hand, in intracellular environment, AuNCs are capable of eliminating the ROS in cells under visible light. For the photocatalyst of GSH protected AuNCs, the photogenerated electrons are in response to reduction reactions, and meanwhile photogenerated holes can oxidize the GSH ligands, protecting other biomolecules from oxidation reactions. This work opens a new gate for the concentration manipulation of ROS in the biological environment as well as the real-time regulation of ROS in organisms.

The LBD11-ROS feedback regulatory loop modulates vascular cambium proliferation and secondary growth in Arabidopsis

Vascular cambium produces the phloem and xylem, vascular tissues that transport resources and provide mechanical support, making it an ideal target for crop improvement. However, much remains unknown about how vascular cambium proliferates. In this study, through pharmaceutical and genetic manipulation of reactive oxygen species (ROS) maxima, we demonstrate a direct link between levels of ROS and activity of LATERAL ORGAN BOUNDARIES DOMAIN 11 (LBD11) in maintaining vascular cambium activity. LBD11 activates the transcription of several key ROS metabolic genes, including PEROXIDASE 71 and RESPIRATORY BURST OXIDASE HOMOLOGS D and F, to generate local ROS maxima in cambium, which in turn enhance the proliferation of cambial cells. In a negative feedback mechanism, higher ROS levels then repress LBD11 expression and maintain the balance of cambial cell proliferation. Our findings thus reveal the role of a novel LBD11/ROS-dependent feedback regulatory system in maintaining vascular cambium-specific redox homeostasis and radial growth in plants.

Role of metal complexes in oxidative stress and ROS generation leading to Cancer

Reactive oxygen species (ROS) are recognized as essential participants in normal cellular processes, while their intricate involvement in the emergence of various diseases, notably cancer, has garnered significant attention. Elevated levels of ROS isassociated with pro-tumorigenic signalling, heightened cell survival, increased proliferation, and DNA damage, thereby making substantial contributions to the genetic instability. Intriguingly, at elevated levels, ROS paradoxically initiate anti-tumorigenic signalling pathways, thereby instigating cell death through oxidative stress. In this comprehensive review, a focus is given on ROS generation, which encompasses both endogenous and exogenous sources that collectively referred to as oxidative stress. To provide a comprehensive understanding, an exploration of the structural, chemical, and biochemical aspects of free radicals is undertaken.Diverse sources contributing to ROS generation, including metal-mediated free radical formation is also discussed. This review additionally conducts an in-depth examination of oxidative stress within the context of cancer. Moreover, noteworthy contributions of key antioxidant enzymes, namely, superoxide dismutase, catalaseand glutathione peroxidase over the multifaceted landscape of carcinogenesis have been discussed, drawing insights from a multitude of studies. Understanding the intricate interplay between pro- and anti-tumorigenic ROS signalling pathways offers a multitude of potential avenues for cancer therapy. The disrupted redox balance observed in cancer cells presents promising opportunities for ROS manipulation, thereby emerging as a viable and innovative treatment strategy. This present review may serve as an invaluable resource, offering profound insights into the multifaceted roles of ROS in cancer while simultaneously highlighting their therapeutic potential, thereby paving the way for novel and effective cancer interventions.

Modulation of Reactive Oxygen Species Homeostasis as a Pleiotropic Effect of Commonly Used Drugs.

Age-associated diseases represent a growing burden for global health systems in our aging society. Consequently, we urgently need innovative strategies to counteract these pathological disturbances. Overwhelming generation of reactive oxygen species (ROS) is associated with age-related damage, leading to cellular dysfunction and, ultimately, diseases. However, low-dose ROS act as crucial signaling molecules and inducers of a vaccination-like response to boost antioxidant defense mechanisms, known as mitohormesis. Consequently, modulation of ROS homeostasis by nutrition, exercise, or pharmacological interventions is critical in aging. Numerous nutrients and approved drugs exhibit pleiotropic effects on ROS homeostasis. In the current review, we provide an overview of drugs affecting ROS generation and ROS detoxification and evaluate the potential of these effects to counteract the development and progression of age-related diseases. In case of inflammation-related dysfunctions, cardiovascular- and neurodegenerative diseases, it might be essential to strengthen antioxidant defense mechanisms in advance by low ROS level rises to boost the individual ROS defense mechanisms. In contrast, induction of overwhelming ROS production might be helpful to fight pathogens and kill cancer cells. While we outline the potential of ROS manipulation to counteract age-related dysfunction and diseases, we also raise the question about the proper intervention time and dosage.

Full-active Cu2O/drug core/shell nanoparticles based on “grafting from” drug coordination polymerization combined with PD-1 blockade for efficient cancer therapy

Precise manipulation of reactive oxygen species (ROS) breakthrough threshold exhibits great potential in destroying solid tumors, reprogramming “immune-cold” tumor and potentiating immunotherapy. However, it is still challenging to develop efficient ROS initiation devices. Herein, we propose a pioneering “grafting from” drug coordination polymerization strategy and develop a fully-coordinated and full-active Cu2O/drug core/shell nanoparticles for multimodal cancer therapy. Chemotherapeutic drug cisplatin (CDDP) and photosensitizer indocyanine green (ICG) were loaded onto the surface of hydrazided hyaluronic acid-decorated Cu2O (HA-Cu2O) nanoparticles through an infinite hydrazide-cisplatin-sulfonic acid coordination mechanism, obtaining CDDP/ICG-coloaded HA-Cu2O (HCCI) nanoplatform. The HCCI nanoplatform exhibited a rapid acid-responsive dissociation behavior and released ICG, Cu+ and CDDP to achieve efficient triple combined photodynamic therapy/chemodynamic therapy/chemotherapy. Importantly, such a combination induced efficient immunogenic cell death cascade mediated by powerful ROS storm to reprogram “immune-cold” tumors and potentiate immunotherapy. The combination of HCCI nanoplatform and αPD-1 not only eradicated primary tumors but effectively inhibited distal tumor growth, lung metastasis and tumor recurrence through reprogramming tumor microenvironment and activating CD8+ T cell antitumor immunity. Collectively, we have presented a drug coordination polymerization loading strategy to develop a robust multimodal antitumor nanoplatform, and this study provides a new direction for the design of nanodrug delivery systems.

Antioxidant Fusion Protein SOD1-Tat Increases the Engraftment Efficiency of Total Bone Marrow Cells in Irradiated Mice.

Total body irradiation is a standard procedure of bone marrow transplantation (BMT) which causes a rapid increase in reactive oxygen species (ROS) in the bone marrow microenvironment during BMT. The increase in ROS reduces the engraftment ability of donor cells, thereby affecting the bone marrow recovery of recipients after BMT. In the early weeks following transplantation, recipients are at high risk of severe infection due to weakened hematopoiesis. Thus, it is imperative to improve engraftment capacity and accelerate bone marrow recovery in BMT recipients. In this study, we constructed recombinant copper/zinc superoxide dismutase 1 (SOD1) fused with the cell-penetrating peptide (CPP), the trans-activator of transcription (Tat), and showed that this fusion protein has penetrating ability and antioxidant activity in both RAW264.7 cells and bone marrow cells in vitro. Furthermore, irradiated mice transplanted with SOD1-Tat-treated total bone marrow donor cells showed an increase in total bone marrow engraftment capacity two weeks after transplantation. This study explored an innovative method for enhancing engraftment efficiency and highlights the potential of CPP-SOD1 in ROS manipulation during BMT.

Oxidative Stress in Cancer Cell Metabolism.

Reactive oxygen species (ROS) are important in regulating normal cellular processes whereas deregulated ROS leads to the development of a diseased state in humans including cancers. Several studies have been found to be marked with increased ROS production which activates pro-tumorigenic signaling, enhances cell survival and proliferation and drives DNA damage and genetic instability. However, higher ROS levels have been found to promote anti-tumorigenic signaling by initiating oxidative stress-induced tumor cell death. Tumor cells develop a mechanism where they adjust to the high ROS by expressing elevated levels of antioxidant proteins to detoxify them while maintaining pro-tumorigenic signaling and resistance to apoptosis. Therefore, ROS manipulation can be a potential target for cancer therapies as cancer cells present an altered redox balance in comparison to their normal counterparts. In this review, we aim to provide an overview of the generation and sources of ROS within tumor cells, ROS-associated signaling pathways, their regulation by antioxidant defense systems, as well as the effect of elevated ROS production in tumor progression. It will provide an insight into how pro- and anti-tumorigenic ROS signaling pathways could be manipulated during the treatment of cancer.

Reactive Oxygen Species and Antitumor Immunity-From Surveillance to Evasion.

The immune system is a crucial regulator of tumor biology with the capacity to support or inhibit cancer development, growth, invasion and metastasis. Emerging evidence show that reactive oxygen species (ROS) are not only mediators of oxidative stress but also players of immune regulation in tumor development. This review intends to discuss the mechanism by which ROS can affect the anti-tumor immune response, with particular emphasis on their role on cancer antigenicity, immunogenicity and shaping of the tumor immune microenvironment. Given the complex role that ROS play in the dynamics of cancer-immune cell interaction, further investigation is needed for the development of effective strategies combining ROS manipulation and immunotherapies for cancer treatment.

The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii.

Dendritic cell is one of the first innate immune cell to encounter T. gondii after the parasite crosses the host intestinal epithelium. T. gondii requires intact DC as a carrier to infiltrate into host central nervous system (CNS) without being detected or eliminated by host defense system. The mechanism by which T. gondii avoids innate immune defense of host cell, especially in the dendritic cell is unknown. Therefore, we examined the role of host PI3K/AKT signaling pathway activation by T. gondii in dendritic cell. T. gondii infection or T. gondii excretory/secretory antigen (TgESA) treatment to the murine dendritic cell line DC2.4 induced AKT phosphorylation, and treatment of PI3K inhibitors effectively suppressed the T. gondii proliferation but had no effect on infection rate or invasion rate. Furthermore, it is found that T. gondii or TgESA can reduce H2O2-induced intracellular reactive oxygen species (ROS) as well as host endogenous ROS via PI3K/AKT pathway activation. While searching for the main source of the ROS, we found that NADPH oxidase 4 (NOX4) expression was controlled by T. gondii infection or TgESA treatment, which is in correlation with previous observation of the ROS reduction by identical treatments. These findings suggest that the manipulation of the host PI3K/AKT signaling pathway and NOX4 expression is an essential mechanism for the down-regulation of ROS, and therefore, for the survival and the proliferation of T. gondii.

Mitochondrial Complex IV Inhibition and Exogenous Oxidants Potently Synergize in Melanoma Cell Death Induction

Due to its functional duality in toxicity as well as signaling, research on therapeutic manipulation of reactive oxygen species (ROS) in cancer has been futile. Targeting melanoma cell death with excess amounts ROS, however, is difficult as these cells are highly resistant towards oxidative stress, creating a need for alternative and combinational approaches. Tumor metabolism mainly relies on aerobic glycolysis. We investigated a potential synergism of mitochondrial complex IV inhibition and exogenous-derived oxidants with both single treatment modalities being essentially non-toxic in melanoma cells. In this study, we investigated murine (metastatic B16F10 and non-metastatic B16F0) as well as human (SK-Mel 28) melanoma cells, and compared them with murine (primary fibroblasts) and human (HaCaT keratinocytes) non-cancer cells. Mitochondrial complex IV inhibition was realized using sodium azide (NaN3) and potassium cyanide (KCN) and pharmacological inhibitor ADDA5. Exogenous oxidants were generated using cell culture medium that has been treated with the cold physical plasma effluent of an atmospheric pressure argon plasma jet (kINPen). This plasma-treated medium was subsequently applied to different cells. Metabolic activity was assessed by fluorescence quantification of resazurin-to-resorufin transformation. ATP levels were monitored by a luminescence assay. Total cell counts, intracellular ROS levels (DCF), mitochondria membrane potential (TMRE), cell membrane integrity (sytox green) and cellular morphology were quantitatively assessed using live cell and high throughput confocal imaging (Operatta; Perkin Elmer). For tumor cells, also 3D spheroid models were investigated for viability by sytox green staining. ADDA5, NaN3 and KCN treatment alone failed to induce a significant alteration in metabolic activity in cancer cells. We then exposed the cells pretreated with NaN3 (100-500 µM) or KCN (250-500 µM) to plasma-treated medium. There was a significant inhibition of metabolic activity and rapid induction of cell death 6 h following treatment in melanoma cells compared to cell receiving plasma-treated medium alone. Increase in cellular superoxide levels and decrease in mitochondrial membrane potential and ATP levels was observed preceding cell death. However, no caspase 3 cleavage was observed upon immunoblotting. siRNA mediated knockdown of COX4a led to increased sensitivity of tumor cells towards plasma-treated medium. Furthermore, we validated our findings using a pharmacological inhibitor of complex IV ADDA5 in a tumor spheroid model and demonstrated that complex IV inhibition supplemented with plasma-treated medium, triggered significant cell death via caspase independent mechanism in melanoma cells.

Role of nerve-muscle interactions and reactive oxygen species in regulation of muscle proteostasis with ageing.

Skeletal muscle ageing is characterised by atrophy, a deficit in specific force generation, increased susceptibility to injury, and incomplete recovery after severe damage. The hypothesis that increased generation of reactive oxygen species (ROS) in vivo plays a key role in the ageing process has been extensively studied, but remains controversial. Skeletal muscle generates ROS at rest and during exercise. ROS can cause oxidative damage particularly to proteins. Indeed, products of oxidative damage accumulate in skeletal muscle during ageing and the ability of muscle cells to respond to increased ROS becomes defective. The aim of this review is to examine the evidence that ROS manipulation in peripheral nerves and/or muscle modifies mechanisms of proteostasis in skeletal muscle and plays a key role in initiating sarcopenia.

Establishing a Low Redox Potential in Giant Yeast Colonies: Effects of Media and Rotation

Abstract Giant yeast colonies develop a low redox potential, which mimics the electrophilic milieu of both the mitochondrial drug metabolizing compartment and the hypoxic core of many tumors. The major metabolic mediators of low redox potential include: ATP, glutathione, NAD+/NADH, and NADP+/NADPH. Ammonia signaling is the critical mechanism that induces stratification of the giant yeast colonies to allow a low redox potential. A comparison of two powerful investigative models for drug pathways using Saccharomyces cerevisiae have been compounded by the use of different growth media and stimuli to the system. Chemogenetic profiling, which uses a pool of yeast deletion mutants to determine survival changes, is heavily slanted to the use of rich media. Giant yeast colonies studies are heavily slanted to the use of poor media. The current study answers the question “what is the difference over time in redox potential, and its major metabolic mediators, between giant yeast colonies grown on rich and poor media?” Using gene deletion tools, we show that cell death in giant yeast colonies is ammonia-dependent. In poor nutrient, ammonia-depleted (Sok2 deletion mutants) giant yeast cultures, rotation can allow manipulation of reactive oxygen species, providing a model to compare high and low redox states without chemical administration. Mechanistically, these changes are not due to detectable NAD/NAPH or NADP/NADPH changes, but are related in changes in glutathione and ATP concentration.

Reactive oxygen species (ROS) and wound healing: the functional role of ROS and emerging ROS-modulating technologies for augmentation of the healing process.

Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.

Defective actin dynamics in dendritic spines: cause or consequence of age-induced cognitive decline?

Ageing is a complex deteriorating process that coincides with changes in metabolism, replicative senescence, increased resistance to apoptosis, as well as progressive mitochondria dysfunction that lead to an increase production and accumulation of reactive oxygen species (ROS). Although controversy on the paradigm of the oxidative damage theory of ageing exists, persuasive studies in Caenorhabditis elegans and yeast have demonstrated that manipulation of ROS can modify the process of ageing and influences the damage of proteins, lipids and DNA. In neurons, ageing impacts on the intrinsic neuronal excitability, it decreases the size of neuronal soma and induces the loss of dendrites and dendritic spines. The actin cytoskeleton is an abundant and broadly expressed system that plays critical functions in many cellular processes ranging from cell motility to controlling cell shape and polarity. It is thus hardly surprising that the expression and the function of actin in neurons is crucial for the morphological changes that occur in the brain throughout life. We propose that alterations in actin filament dynamics in dendritic spines may be one of the key events contributing to the initial phases of ageing in the brain.

Actin as Deathly Switch? How Auxin Can Suppress Cell-Death Related Defence

Plant innate immunity is composed of two layers – a basal immunity, and a specific effector-triggered immunity, which is often accompanied by hypersensitive cell death. Initiation of cell death depends on a complex network of signalling pathways. The phytohormone auxin as central regulator of plant growth and development represents an important component for the modulation of plant defence. In our previous work, we showed that cell death is heralded by detachment of actin from the membrane. Both, actin response and cell death, are triggered by the bacterial elicitor harpin in grapevine cells. In this study we investigated, whether harpin-triggered actin bundling is necessary for harpin-triggered cell death. Since actin organisation is dependent upon auxin, we used different auxins to suppress actin bundling. Extracellular alkalinisation and transcription of defence genes as the basal immunity were examined as well as cell death. Furthermore, organisation of actin was observed in response to pharmacological manipulation of reactive oxygen species and phospholipase D. We find that induction of defence genes is independent of auxin. However, auxin can suppress harpin-induced cell death and also counteract actin bundling. We integrate our findings into a model, where harpin interferes with an auxin dependent pathway that sustains dynamic cortical actin through the activity of phospholipase D. The antagonism between growth and defence is explained by mutual competition for signal molecules such as superoxide and phosphatidic acid. Perturbations of the auxin-actin pathway might be used to detect disturbed integrity of the plasma membrane and channel defence signalling towards programmed cell death.