Auxins are plant hormones that play a central role in controlling plant growth and development across different environmental conditions. Even at low concentrations, auxins can regulate gene ...expression through specific transcription factors and proteins that are modulated to environmental responses in the signalling cascade. Auxins are synthesized in tissues with high cell division activity and distributed by specific transmembrane proteins that regulate efflux and influx. This review presents recent advances in understanding the biosynthetic pathways, both dependent and independent of tryptophan, highlighting the intermediate indole compounds (indole‐3‐acetamide, indole‐3‐acetaldoxime, indole‐3‐pyruvic acid and tryptamine) and the key enzymes for auxin biosynthesis, such as YUCs and TAAs. In relation to the signalling cascade, it has been shown that auxins influence gene expression regulation by the connection between synthesis and distribution. Moreover, the molecular action of the auxin response factors and auxin/indole‐3‐acetic acid transcription factors with the F‐box TIR1/AFB auxin receptors regulates gene expression. In addition, the importance of microRNAs in the auxin signalling pathway and their influence on plant plasticity to environmental fluctuations is also demonstrated. Finally, this review describes the chemical and biological processes involving auxins in plants.
Auxin‐integrating chemical and molecular processes are involved in plant growth and development, regulated by the synthesis and distribution of the phytohormon.
Vascular calcification (VC), which is categorized by intimal and medial calcification, depending on the site(s) involved within the vessel, is closely related to cardiovascular disease. Specifically, ...medial calcification is prevalent in certain medical situations, including chronic kidney disease and diabetes. The past few decades have seen extensive research into VC, revealing that the mechanism of VC is not merely a consequence of a high-phosphorous and -calcium milieu, but also occurs via delicate and well-organized biologic processes, including an imbalance between osteochondrogenic signaling and anticalcific events. In addition to traditionally established osteogenic signaling, dysfunctional calcium homeostasis is prerequisite in the development of VC. Moreover, loss of defensive mechanisms, by microorganelle dysfunction, including hyper-fragmented mitochondria, mitochondrial oxidative stress, defective autophagy or mitophagy, and endoplasmic reticulum (ER) stress, may all contribute to VC. To facilitate the understanding of vascular calcification, across any number of bioscientific disciplines, we provide this review of a detailed updated molecular mechanism of VC. This encompasses a vascular smooth muscle phenotypic of osteogenic differentiation, and multiple signaling pathways of VC induction, including the roles of inflammation and cellular microorganelle genesis.
Alzheimer disease (AD) is a frequent and devastating neurodegenerative disease in humans, but still no curative treatment has been developed. Although many explicative theories have been proposed, ...precise pathophysiological mechanisms are unknown. Due to the importance of astrocytes in brain homeostasis they have become interesting targets for the study of AD. Changes in astrocyte function have been observed in brains from individuals with AD, as well as in AD
and
animal models. The presence of amyloid beta (Aβ) has been shown to disrupt gliotransmission, neurotransmitter uptake, and alter calcium signaling in astrocytes. Furthermore, astrocytes express apolipoprotein E and are involved in the production, degradation and removal of Aβ. As well, changes in astrocytes that precede other pathological characteristics observed in AD, point to an early contribution of astroglia in this disease. Astrocytes participate in the inflammatory/immune responses of the central nervous system. The presence of Aβ activates different cell receptors and intracellular signaling pathways, mainly the advanced glycation end products receptor/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway, responsible for the transcription of pro-inflammatory cytokines and chemokines in astrocytes. The release of these pro-inflammatory agents may induce cellular damage or even stimulate the production of Aβ in astrocytes. Additionally, Aβ induces the appearance of oxidative stress (OS) and production of reactive oxygen species and reactive nitrogen species in astrocytes, affecting among others, intracellular calcium levels, NADPH oxidase (NOX), NF-κB signaling, glutamate uptake (increasing the risk of excitotoxicity) and mitochondrial function. Excessive neuroinflammation and OS are observed in AD, and astrocytes seem to be involved in both. The Aβ/NF-κB interaction in astrocytes may play a central role in these inflammatory and OS changes present in AD. In this paper, we also discuss therapeutic measures highlighting the importance of astrocytes in AD pathology. Several new therapeutic approaches involving phenols (curcumin), phytoestrogens (genistein), neuroesteroids and other natural phytochemicals have been explored in astrocytes, obtaining some promising results regarding cognitive improvements and attenuation of neuroinflammation. Novel strategies comprising astrocytes and aimed to reduce OS in AD have also been proposed. These include estrogen receptor agonists (pelargonidin), Bambusae concretio Salicea, Monascin, and various antioxidatives such as resveratrol, tocotrienol, anthocyanins, and epicatechin, showing beneficial effects in AD models.
Perylenequinones (PQs) are natural photosensitizing compounds used as photodynamic therapy, and heat stress (HS) is the main limiting factor of mycelial growth and secondary metabolism of fungi. This ...study aimed to unravel the impact of HS-induced Ca
2+
and the calcium signaling pathway on PQ biosynthesis of
Shiraia
sp. Slf14(w). Meanwhile, the intricate interplay between HS-induced NO and Ca
2+
and the calcium signaling pathway was investigated. The outcomes disclosed that Ca
2+
and the calcium signaling pathway activated by HS could effectively enhance the production of PQs in
Shiraia
sp. Slf14(w). Further investigations elucidated the specific mechanism through which NO signaling molecules induced by HS act upon the Ca
2+
/CaM (calmodulin) signaling pathway, thus propelling PQ biosynthesis in
Shiraia
sp. Slf14(w). This was substantiated by decoding the downstream positioning of the CaM/CaN (calcineurin) pathway in relation to NO through comprehensive analyses encompassing transcript levels, enzyme assays, and the introduction of chemical agents. Concurrently, the engagement of Ca
2+
and the calcium signaling pathway in heat shock signaling was also evidenced. The implications of our study underscore the pivotal role of HS-induced Ca
2+
and the calcium signaling pathway, which not only participate in heat shock signal transduction but also play an instrumental role in promoting PQ biosynthesis. Consequently, our study not only enriches our comprehension of the mechanisms driving HS signaling transduction in fungi but also offers novel insights into the PQ synthesis paradigm within
Shiraia
sp. Slf14(w).
Key points
• The calcium signaling pathway was proposed to participate in PQ biosynthesis under HS.
• HS-induced NO was revealed to act upon the calcium signaling pathway for the first time.
Despite the use of sorafenib as one of the most effective drugs for the treatment of liver cancer, its significant limitations remain—poor solubility, the need to use high doses with the ensuing ...complications on healthy tissues and organs, and the formation of cell resistance to the drug. At the same time, there is more and more convincing evidence of the anticancer effect of selenium-containing compounds and nanoparticles. The aim of this work was to develop a selenium–sorafenib nanocomplex and study the molecular mechanisms of its anticancer effect on human hepatocyte carcinoma cells, where nanoselenium is not only a sorafenib transporter, but also an active compound. We have created a selenium–sorafenib nanocomplex based on selenium nanoparticles with size 100 nm. Using vitality tests, fluorescence microscopy, and PCR analysis, it was possible to show that selenium nanoparticles, both by themselves and doped with sorafenib, have a pronounced pro-apoptotic effect on HepG2 cells with an efficiency many times greater than that of sorafenib (So). “Naked” selenium nanoparticles (SeNPs) and the selenium–sorafenib nanocomplex (SeSo), already after 24 h of exposure, lead to the induction of the early stages of apoptosis with the transition to the later stages with an increase in the incubation time up to 48 h. At the same time, sorafenib, at the studied concentrations, began to exert a proapoptotic effect only after 48 h. Under the action of SeNPs and SeSo, both classical pathways of apoptosis induction and ER-stress-dependent pathways involving Ca2+ ions are activated. Thus, sorafenib did not cause the generation of Ca2+ signals by HepG2 cells, while SeNPs and SeSo led to the activation of the Ca2+ signaling system of cells. At the same time, the selenium–sorafenib nanocomplex turned out to be more effective in activating the Ca2+ signaling system of cells, inducing apoptosis and ER stress by an average of 20–25% compared to “naked” selenium nanoparticles. Our data on the mechanisms of action and the created nanocomplex are promising as a platform for the creation of highly selective and effective drugs with targeted delivery to tumors.
The mediation of volatile secondary metabolites in signalling between plants and other organisms has long been seen as presenting opportunities for sustainable crop protection. Initially, ...exploitation of interactions between plants and other organisms, particularly insect pests, foundered because of difficulties in delivering, sustainably, the signal systems for crop protection. We now have mounting and, in some cases, clear practical evidence for successful delivery by companion cropping or next-generation genetic modification (GM). At the same time, the type of plant signalling being exploited has expanded to signalling from plants to organisms antagonistic to pests, and to plant stress-induced, or primed, plant-to-plant signaling for defence and growth stimulation.
Probiotics can effectively modulate host immune responses and prevent gastrointestinal diseases. The objective of this study was to investigate the probiotic characteristics of Lactobacillus brevis ...KU15152 isolated from kimchi and its protective potential against intestinal inflammation induced by Staphylococcus aureus lipoteichoic acid (aLTA). L. brevis KU15152 exhibited a high survival rate in artificial gastric and bile environments. Additionally, the adhesion capability of the strain to HT-29 cells was higher than that of L. rhamnosus GG. L. brevis KU15152 did not produce harmful enzymes, such as β-glucuronidase, indicating that it could be used as a potential probiotic. The antiinflammatory potential of L. brevis KU15152 was determined in HT-29 cells. Treatment with L. brevis KU15152 suppressed the production of interleukin-8 without inducing significant cytotoxicity. The downregulatory effects of L. brevis KU15152 were involved in the suppression of nuclear factorkappa B activation mediated by the extracellular signal-regulated kinase and Akt signaling pathways. Collectively, these data suggest that L. brevis KU15152 can be used in developing therapeutic and prophylactic products to manage and treat aLTA-induced intestinal damage.
Key points
Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists.
Intracellular Ca2+ overload, increased reactive oxygen species ...(ROS) production, mitochondrial damage and intra‐acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis.
Transient receptor potential melastatin 2 (TRPM2) is a non‐selective cation channel that has recently emerged as an important contributor to oxidative‐stress‐induced cellular Ca2+ overload across different diseases.
We demonstrated that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2O2 treatment and contributed to bile acid‐induced extracellular Ca2+ influx in acinar cells, which promoted acinar cell necrosis in vitro and in vivo.
These results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.
Acute biliary pancreatitis poses a significant clinical challenge as currently no specific pharmaceutical treatment exists. Disturbed intracellular Ca2+ signalling caused by bile acids is a hallmark of the disease, which induces increased reactive oxygen species (ROS) production, mitochondrial damage, intra‐acinar digestive enzyme activation and cell death. Because of this mechanism of action, prevention of toxic cellular Ca2+ overload is a promising therapeutic target. Transient receptor potential melastatin 2 (TRPM2) is a non‐selective cation channel that has recently emerged as an important contributor to oxidative‐stress‐induced cellular Ca2+ overload across different diseases. However, the expression and possible functions of TRPM2 in the exocrine pancreas remain unknown. Here we found that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2O2 treatment. TRPM2 activity was found to contribute to bile acid‐induced extracellular Ca2+ influx in acinar cells, but did not have the same effect in ductal cells. The generation of intracellular ROS in response to bile acids was remarkably higher in pancreatic acinar cells compared to isolated ducts, which can explain the difference between acinar and ductal cells. This activity promoted acinar cell necrosis in vitro independently from mitochondrial damage or mitochondrial fragmentation. In addition, bile‐acid‐induced experimental pancreatitis was less severe in TRPM2 knockout mice, whereas the lack of TRPM2 had no protective effect in cerulein‐induced acute pancreatitis. Our results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.
Key points
Acute biliary pancreatitis is a significant clinical challenge as currently no specific pharmaceutical treatment exists.
Intracellular Ca2+ overload, increased reactive oxygen species (ROS) production, mitochondrial damage and intra‐acinar digestive enzyme activation caused by bile acids are hallmarks of acute biliary pancreatitis.
Transient receptor potential melastatin 2 (TRPM2) is a non‐selective cation channel that has recently emerged as an important contributor to oxidative‐stress‐induced cellular Ca2+ overload across different diseases.
We demonstrated that TRPM2 is expressed in the plasma membrane of mouse pancreatic acinar and ductal cells, which can be activated by increased oxidative stress induced by H2O2 treatment and contributed to bile acid‐induced extracellular Ca2+ influx in acinar cells, which promoted acinar cell necrosis in vitro and in vivo.
These results suggest that the inhibition of TRPM2 may be a potential treatment option for biliary pancreatitis.
Summary
Spinal cord injury (SCI) is a major disability requiring more effective treatment than is currently available. MicroRNAs have been shown to effectively regulate gene expression at the ...translational level. The aim of the present study was to explore the potential role of miR‐30‐5p and possible mechanism in SCI. We found that miR‐30‐5p was notably down‐regulated, while Neurod 1 expression was highly elevated in microglia from the mouse model of SCI. Additionally, overexpression of miR‐30a‐5p significantly suppressed inflammatory responses as reflected by a decrease in the secretion of the cytokines TNF‐α, IL‐1β and IL‐10 triggered by SCI. Furthermore, introduction of miR‐30a‐5p strengthened the scavenging of oxygen free radicals accompanied by an increase in the expression of SEPN1, TXNL1 and GPX1. More importantly, our study explored that Neurod 1 was a direct and functional target of miR‐30a‐5p, which was validated by the dual luciferase reporter assay. qRT‐PCR and western blot analysis further validated that miR‐30a‐5p negatively regulated the expression of Neurod 1. Mechanistically, overexpression of miR‐30a‐5p or silencing of the Neurod 1 gene prevented the MAPK/ERK signalling and inhibited inflammatory responses, meanwhile activated SEPN1, TXNL1 and GPX1. These findings indicate that miR‐30a‐5p ameliorates inflammatory responses and oxidative stress by targeting Neurod 1 through MAPK/ERK signalling.
Organisms must respond to hypoxia to preserve oxygen homeostasis. We identify a thiol oxidase, previously assigned as cysteamine (2-aminoethanethiol) dioxygenase (ADO), as a low oxygen affinity ...(high-
O
) amino-terminal cysteine dioxygenase that transduces the oxygen-regulated stability of proteins by the N-degron pathway in human cells. ADO catalyzes the conversion of amino-terminal cysteine to cysteine sulfinic acid and is related to the plant cysteine oxidases that mediate responses to hypoxia by an identical posttranslational modification. We show in human cells that ADO regulates RGS4/5 (regulator of G protein signaling) N-degron substrates, modulates G protein-coupled calcium ion signals and mitogen-activated protein kinase activity, and that its activity extends to other N-cysteine proteins including the angiogenic cytokine interleukin-32. Identification of a conserved enzymatic oxygen sensor in multicellular eukaryotes opens routes to better understanding and therapeutic targeting of adaptive responses to hypoxia.
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