Glucagon Receptor Antagonist for Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is an emerging major unmet need and one of the most significant clinic challenges in cardiology. The pathogenesis of HFpEF is associated with multiple risk factors. Hypertension and metabolic disorders associated with obesity are the 2 most prominent comorbidities observed in patients with HFpEF. Although hypertension-induced mechanical overload has long been recognized as a potent contributor to heart failure with reduced ejection fraction, the synergistic interaction between mechanical overload and metabolic disorders in the pathogenesis of HFpEF remains poorly characterized. METHOD: We investigated the functional outcome and the underlying mechanisms from concurrent mechanic and metabolic stresses in the heart by applying transverse aortic constriction in lean C57Bl/6J or obese/diabetic B6.Cg-Lepob/J (ob/ob) mice, followed by single-nuclei RNA-seq and targeted manipulation of a top-ranked signaling pathway differentially affected in the 2 experimental cohorts. RESULTS: In contrast to the post-trans-aortic constriction C57Bl/6J lean mice, which developed pathological features of heart failure with reduced ejection fraction over time, the post-trans-aortic constriction ob/ob mice showed no significant changes in ejection fraction but developed characteristic pathological features of HFpEF, including diastolic dysfunction, worsened cardiac hypertrophy, and pathological remodeling, along with further deterioration of exercise intolerance. Single-nuclei RNA-seq analysis revealed significant transcriptome reprogramming in the cardiomyocytes stressed by both pressure overload and obesity/diabetes, markedly distinct from the cardiomyocytes singularly stressed by pressure overload or obesity/diabetes. Furthermore, glucagon signaling was identified as the top-ranked signaling pathway affected in the cardiomyocytes associated with HFpEF. Treatment with a glucagon receptor antagonist significantly ameliorated the progression of HFpEF-related pathological features in 2 independent preclinical models. Importantly, cardiomyocyte-specific genetic deletion of the glucagon receptor also significantly improved cardiac function in response to pressure overload and metabolic stress. CONCLUSIONS: These findings identify glucagon receptor signaling in cardiomyocytes as a critical determinant of HFpEF progression and provide proof-of-concept support for glucagon receptor antagonism as a potential therapy for the disease.

Kielin/chordin-like protein deficiency aggravates pressure overload-induced cardiac dysfunction and remodeling via P53/P21/CCNB1 signaling in mice.

Targeting cardiac remodeling is regarded as a key therapeutic strategy for heart failure. Kielin/chordin-like protein (KCP) is a secretory protein with 18 cysteine-rich domains and associated with kidney and liver fibrosis. However, the relationship between KCP and cardiac remodeling remains unclear. Here, we aimed to investigate the role of KCP in cardiac remodeling induced by pressure overload and explore its potential mechanisms. Left ventricular (LV) KCP expression was measured with real-time quantitative PCR, western blotting, and immunofluorescence staining in pressure overload-induced cardiac remodeling in mice. Cardiac function and remodeling were evaluated in wide-type (WT) mice and KCP knockout (KO) mice by echocardiography, which were further confirmed by histological analysis with hematoxylin and eosin and Masson staining. RNA sequence was performed with LV tissue from WT and KO mice to identify differentially expressed genes and related signaling pathways. Primary cardiac fibroblasts (CFs) were used to validate the regulatory role and potential mechanisms of KCP during fibrosis. KCP was down-regulated in the progression of cardiac remodeling induced by pressure overload, and was mainly expressed in fibroblasts. KCP deficiency significantly aggravated pressure overload-induced cardiac dysfunction and remodeling. RNA sequence revealed that the role of KCP deficiency in cardiac remodeling was associated with cell division, cell cycle, and P53 signaling pathway, while cyclin B1 (CCNB1) was the most significantly up-regulated gene. Further investigation in vivo and in vitro suggested that KCP deficiency promoted the proliferation of CFs via P53/P21/CCNB1 pathway. Taken together, these results suggested that KCP deficiency aggravates cardiac dysfunction and remodeling induced by pressure overload via P53/P21/CCNB1 signaling in mice.

TRPA1 deficiency aggravates dilated cardiomyopathy by promoting S100A8 expression to induce M1 macrophage polarization in rats.

Transient receptor potential ankyrin 1 (TRPA1) plays an important role in different cardiovascular diseases. However, the role of TRPA1 in dilated cardiomyopathy (DCM) remains unclear. Here, we aimed to investigate the role of TRPA1 in DCM induced by doxorubicin (DOX) and explore its possible mechanisms. GEO data were used to explore the expression of TRPA1 in DCM patients. DOX (2.5 mg/kg/week, 6 weeks, i.p.) was used to induce DCM. Bone marrow-derived macrophages (BMDMs) and neonatal rat cardiomyocytes (NRCMs) were isolated to explore the role of TRPA1 in macrophage polarization, cardiomyocyte apoptosis, and pyroptosis. In addition, DCM rats were treated with the TRPA1 activator, cinnamaldehyde to explore the possibility of clinical translation. TRPA1 expression was increased in left ventricular (LV) tissue in DCM patients and rats. TRPA1 deficiency aggravated the cardiac dysfunction, cardiac injury, and LV remodeling in DCM rats. In addition, TRPA1 deficiency promoted the M1 macrophage polarization, oxidative stress, cardiac apoptosis, and pyroptosis induced by DOX. RNA-seq results showed that TRPA1 knockout promoted the expression of S100A8, an inflammatory molecule that belongs to the family of Ca2+ -binding S100 proteins, in DCM rats. Furthermore, S100A8 inhibition attenuated M1 macrophage polarization in BMDMs isolated from TRPA1 deficiency rats. Recombinant S100A8 promoted the apoptosis, pyroptosis, and oxidative stress in primary cardiomyocytes stimulated with DOX. Finally, TRPA1 activation via cinnamaldehyde alleviated the cardiac dysfunction and reduced S100A8 expression in DCM rats. Taken together, these results suggested that TRPA1 deficiency aggravates DCM by promoting S100A8 expression to induce M1 macrophage polarization and cardiac apoptosis.

Identification of two plastid transit peptides for construction of pollen-inactivation system in rice.

Hybrid seed production technology (SPT) is achieved through the utilization of a recessive nuclear male-sterile mutant transformed with a transgenic cassette comprising three essential components: the wild-type gene to restore the fertility of the male-sterile mutant, an α-amylase gene to disrupt transgenic pollen grains, and red fluorescence protein gene DsRed to distinguish the transgenic seeds from the nontransgenic male sterile seeds. In rice, we establish the pollen disruption system by introducing an amyloplast targeting signal peptide (ASP) at the N-terminus of maize α-amylase protein ZM-AA1ΔSP (ZM-AA1 with the N-terminal signal peptide removed). The ASP facilitates the transport of ZM-AA1ΔSP protein into amyloplast where it degrades starch, resulting in disruption of the pollen fertility. To obtain such signal peptides for rice, we searched the rice proteins homologous to the defined wheat amyloplast proteins followed by protein-protein interaction network predictions and targeting signal peptides prediction. These analyses enabled the identification of four candidate ASPs in rice, which were designated as ASP1, ASP2, ASP3, and ASP4, respectively. ASP1 and ASP2, when linked with ZM-AA1ΔSP, exhibited the capability to disrupt transgenic pollen grains, whereas ASP3 and ASP4 did not produce this effect. Interestingly, the localization experiments showed that ASP3 and ASP4 were able to target the proteins into chloroplast. The ASP1 and ASP2 sequences provide valuable tools for genetic engineering of the rice male-sterile system, which will contribute to the hybrid rice breeding and production. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01471-y.

Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling.

Immune response plays a crucial role in post-myocardial infarction (MI) myocardial remodeling. Neogenin (Neo1), a multifunctional transmembrane receptor, plays a critical role in the immune response; however, whether Neo1 participates in pathological myocardial remodeling after MI is unclear. Our study found that Neo1 expression changed significantly after MI in vivo and after LPS + IFN-γ stimulation in bone marrow-derived macrophages (BMDMs) in vitro. Neo1 functional deficiency (using a neutralizing antibody) and macrophage-specific Neo1 deficiency (induced by Neo1flox/flox;Cx3cr1cre mice) increased infarction size, enhanced cardiac fibrosis and cardiomyocyte apoptosis, and exacerbated left ventricular dysfunction post-MI in mice. Mechanistically, Neo1 deficiency promoted macrophage infiltration into the ischemic myocardium and transformation to a proinflammatory phenotype, subsequently exacerbating the inflammatory response and impairing inflammation resolution post-MI. Neo1 deficiency regulated macrophage phenotype and function, possibly through the JAK1-STAT1 pathway, as confirmed in BMDMs in vitro. Blocking the JAK1-STAT1 pathway with fludarabine phosphate abolished the impact of Neo1 on macrophage phenotype and function, inflammatory response, inflammation resolution, cardiomyocyte apoptosis, cardiac fibrosis, infarction size and cardiac function. In conclusion, Neo1 deficiency aggravates inflammation and left ventricular remodeling post-MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway. These findings highlight the anti-inflammatory potential of Neo1, offering new perspectives for therapeutic targets in MI treatment. Neo1 deficiency aggravated inflammation and left ventricular remodeling after MI by modulating macrophage phenotypes and functions via the JAK1-STAT1 signaling pathway.

Unveiling the Origin of Co3 O4 Quantum Dots for Photocatalytic Overall Water Splitting.

Spinel cobalt oxide displays excellent photocatalytic performance, especially in solar driven water oxidation. However, the process of water reduction to hydrogen is considered as the Achilles' heel of solar water splitting over Co3 O4 owing to its low conduction band. Enhancement of the water splitting efficiency using Co3 O4 requires deeper insights of the carrier dynamics during water splitting process. Herein, the carrier dynamic kinetics of colloidal Co3 O4 quantum dots-Pt hetero-junctions is studied, which mimics the hydrogen reduction process during water splitting. It is showed that the quantum confinement effect induced by the small QD size raised the conduction band edge position of Co3 O4 QDs, so that the ligand-to-metal charge transfer from 2p state of oxygen to 3d state of Co2+ occurs, which is necessary for overall water splitting and cannot be achieved in Co3 O4 bulk crystals. The findings in this work provide insights of the photocatalytic mechanism of Co3 O4 catalysts and benefit rational design of Co3 O4 -based photocatalytic systems.

The role of semaphorins in cardiovascular diseases: Potential therapeutic targets and novel biomarkers.

Semaphorins (Semas), which belongs to the axonal guidance molecules, include 8 classes and could affect axon growth in the nervous system. Recently, semaphorins were found to regulate other pathophysiological processes, such as immune response, oncogenesis, tumor angiogenesis, and bone homeostasis, through binding with their plexin and neuropilin receptors. In this review, we summarized the detailed role of semaphorins and their receptors in the pathological progression of various cardiovascular diseases (CVDs), highlighting that semaphorins may be potential therapeutic targets and novel biomarkers for CVDs.

Resolvin D2 and its receptor GPR18 in cardiovascular and metabolic diseases: A promising biomarker and therapeutic target.

Accumulating evidence suggests that inflammation plays an important role in the pathophysiology of the initiation and progression of cardiovascular and metabolic diseases (CVMDs). Anti-inflammation strategies and those that promote inflammation resolution have gradually become potential therapeutic approaches for CVMDs. Resolvin D2 (RvD2), a specialized pro-resolving mediator, exerts anti-inflammatory and pro-resolution effects through its receptor GPR18, a G protein-coupled receptor. Recently, the RvD2/GPR18 axis has received more attention due to its protective role in CVMDs, including atherosclerosis, hypertension, ischaemiareperfusion, and diabetes. Here, we introduce basic information about RvD2 and GPR18, summarize their roles in different immune cells, and review the therapeutic potential of the RvD2/GPR18 axis in CVMDs. In summary, RvD2 and its receptor GPR18 play an important role in the occurrence and development of CVMDs and are potential biomarkers and therapeutic targets.

Maresin-1 and its receptors RORα/LGR6 as potential therapeutic target for respiratory diseases.

Maresin-1 is one of the representative specialized pro-resolving mediators that has shown beneficial effects in inflammatory disease models. Recently, two distinct types of receptor molecules were discovered as the targets of maresin-1, further revealing the pro-resolution mechanism of maresin-1. One is retinoic acid-related orphan receptor α (RORα) and the another one is leucine-rich repeat domain-containing G protein-coupled receptor 6 (LGR6). In this review, we summarized the detailed role of maresin-1 and its two different receptors in respiratory diseases. RORα and LGR6 are potential targets for the treatment of respiratory diseases. Future basic research and clinical trials on MaR1 and its receptors should provide useful information for the treatment of respiratory diseases.

Atomically Dispersed Janus Nickel Sites on Red Phosphorus for Photocatalytic Overall Water Splitting.

Single-atom nickel catalysts hold great promise for photocatalytic water splitting due to their plentiful active sites and cost-effectiveness. Herein, we adopt a reactive-group guided strategy to prepare atomically dispersed nickel catalysts on red phosphorus. The hydrothermal treatment of red phosphorus leads to the formation of P-H and P-OH groups, which behave as the reactive functionalities to generate the dual structure of single-atom P-Ni and P-O-Ni catalytic sites. The produced single-atom sites provide two different functions: P-Ni for water reduction and P-O-Ni for water oxidation. Benefitting from this specific Janus structure, Ni-red phosphorus shows an elevated hydrogen evolution rate compared to Ni nanoparticle-modified red phosphorus under visible-light irradiation. The hydrogen evolution rate was additionally enhanced with increased reaction temperature, reaching 91.51 µmol h-1 at 70 °C, corresponding to an apparent quantum efficiency of 8.9 % at 420 nm excitation wavelength.

Efficient Synthesis of Folate-Conjugated Hollow Polymeric Capsules for Accurate Drug Delivery to Cancer Cells.

This study presents an efficient and systematic approach to synthesize bioapplicable porous hollow polymeric capsules (HPCs). The hydroxyl-functionalized nanoporous polymers with hollow capsular shapes could be generated via the moderate Friedel-Crafts reaction without using any hard or soft template. The numerous primitive hydroxyl groups on these HPCs were further converted to carboxyl groups. Owing to the abundance of highly branched carboxyl groups on the surface of the HPCs, biomolecules [such as folic acid (FA)] could be covalently decorated on these organic capsules (FA-HPCs) for drug delivery applications. The intrinsic hollow porosities and specific targeting agent offered a maximum drug encapsulation efficiency of up to 86% and drug release of up to 50% in 30 h in an acidic environment. The in vitro studies against cancer cells demonstrated that FA-HPCs exhibited a more efficient cellular uptake and intracellular doxorubicin release than bare HPCs. This efficient approach to fabricate carbonyl-functionalized hollow organic capsules may open avenues for a new type of morphological-controlled nanoporous polymers for various potential bioengineering applications.

The Association between Obesity and Severity in Patients with Coronavirus Disease 2019: a Retrospective, Single-center Study, Wuhan.

Aim: In other respiratory infectious diseases, obesity may be associated with a poor outcome. For coronavirus disease 2019 (COVID-19), the association between obesity and severity or prognosis requires further analysis. Methods: This was a retrospective, single-center study. Hospitalized patients were recruited in Renmin Hospital of Wuhan University from January 2, 2020 to February 20, 2020. The data of body mass index (BMI) was obtained from follow-up of surviving patients. According to BMI, normal weight was defined as 18.5-23.9 kg/m2, overweight as 24.0-27.9 kg/m2 and obesity as > 28.0 kg/m2. Results: A total of 463 patients were enrolled, of which 242 (52.3%) patients were in the normal weight group; 179 (38.7%) were in the overweight group; and 42 (9.1%) were in the obesity group. Compared to the normal group, obese patients were more likely to have a higher heart rate; lower finger oxygen saturation; higher levels of white blood cells, neutrophil counts, basophil counts, intravenous glucose, triacylglycerol, uric acid, alanine aminotransferase, creatine kinase-MB, CD19+ cell counts and percentage; and lower levels of monocyte percentage, high density lipoprotein and CD3+ cell percentage. In addition, the proportions of hypertension (21.5% vs. 42.6%) and severe+critical illness (47.8 vs. 81.0 %) were significantly higher in the obesity group than those in normal group. However, no significant differences were observed between the normal and obesity groups in critical illness, organ damage and defined endpoint (mechanical ventilation or intensive care unit). Multiple logistic regression showed that obesity increased the risk of developing severe+critical illness (Odd ratio 3.586, 95% CI 1.550-8.298, P=0.003) in patients with COVID-19, and did not affect the risk of critical illness, organ damage and endpoints. Overweight did not affect the risk of severity, organ damage or endpoint in patients with COVID-19. Conclusion: Obesity may be a risk factor for developing severity in patients with COVID-19.

The Expression of IL-12 Family Members in Patients with Hypertension and Its Association with the Occurrence of Carotid Atherosclerosis.

BACKGROUND: The interleukin-12 (IL-12) family consists of four members, namely, IL-12, IL-23, IL-27, and IL-35. The aim of this study was to examine the expression of circulating IL-12, IL-23, IL-27, and IL-35 in hypertensive patients. METHODS: Blood samples were collected from hypertensive patients and nonhypertensive (control) subjects, and protein multifactorial monitor kits were used to measure the plasma IL-12, IL-23, IL-27, and IL-35 levels in each sample. In addition, all enrolled subjects underwent ambulatory blood pressure monitoring (ABPM) and vascular stiffness. RESULTS: Hypertensive patients exhibited higher IL-12, IL-23, and IL-27 levels and lower IL-35 levels than control subjects; IL-12, IL-23, and IL-27 levels were positively correlated with both systolic blood pressure (SBP) and diastolic blood pressure (DBP), while IL-35 levels were negatively correlated with SBP and DBP. IL-12, IL-23, and IL-27 levels gradually increased in patients with grade I, II, and III hypertension, while IL-35 levels gradually reduced. According to the ABPM results, hypertensive patients were divided into the dipper and nondipper hypertension groups; IL-12, IL-23, IL-27, and IL-35 levels showed no differences between the two groups, but IL-12, IL-23, and IL-27 levels in both groups increased compared with those in the control group, while IL-35 levels decreased. Additionally, the expression of these IL-12 family members was influenced by many clinical factors and was independently associated with the occurrence of carotid atherosclerotic plaques. CONCLUSIONS: The changes in IL-12, IL-23, IL-27, and IL-35 levels were not associated with the presence of the nondipper type but were closely associated with the development of carotid atherosclerotic plaque in hypertensive patients.

Identification of late-stage pollen-specific promoters for construction of pollen-inactivation system in rice.

Large-scale production of male sterile seeds can be achieved by introducing a fertility-restoration gene linked with a pollen-killer gene into a recessive male sterile mutant. We attempted to construct this system in rice by using a late-stage pollen-specific (LSP) promoter driving the expression of maize α-amylase gene ZM-AA1. To obtain such promoters in rice, we conducted comparative RNA-seq analysis of mature pollen with meiosis anther, and compared this with the transcriptomic data of various tissues in the Rice Expression Database, resulting in 269 candidate LSP genes. Initial test of nine LSP genes showed that only the most active OsLSP3 promoter could drive ZM-AA1 to disrupt pollen. We then analyzed an additional 22 LSP genes and found 12 genes stronger than OsLSP3 in late-stage anthers. The promoters of OsLSP5 and OsLSP6 showing higher expression than OsLSP3 at stages 11 and 12 could drive ZM-AA1 to inactivate pollen, while the promoter of OsLSP4 showing higher expression at stage 12 only could not drive ZM-AA1 to disrupt pollen, suggesting that strong promoter activity at stage 11 was critical for pollen inactivation. The strong pollen-specific promoters identified in this study provided valuable tools for genetic engineering of rice male sterile system for hybrid rice production.

GDSL esterase/lipases OsGELP34 and OsGELP110/OsGELP115 are essential for rice pollen development.

Pollen exine contains complex biopolymers of aliphatic lipids and phenolics. Abnormal development of pollen exine often leads to plant sterility. Molecular mechanisms regulating exine formation have been studied extensively but remain ambiguous. Here we report the analyses of three GDSL esterase/lipase protein genes, OsGELP34, OsGELP110, and OsGELP115, for rice exine formation. OsGELP34 was identified by cloning of a male sterile mutant gene. OsGELP34 encodes an endoplasmic reticulum protein and was mainly expressed in anthers during pollen exine formation. osgelp34 mutant displayed abnormal exine and altered expression of a number of key genes required for pollen development. OsGELP110 was previously identified as a gene differentially expressed in meiotic anthers. OsGELP110 was most homologous to OsGELP115, and the two genes showed similar gene expression patterns. Both OsGELP110 and OsGELP115 proteins were localized in peroxisomes. Individual knockout of OsGELP110 and OsGELP115 did not affect the plant fertility, but double knockout of both genes altered the exine structure and rendered the plant male sterile. OsGELP34 is distant from OsGELP110 and OsGELP115 in sequence, and osgelp34 and osgelp110/osgelp115 mutants were different in anther morphology despite both were male sterile. These results suggested that OsGELP34 and OsGELP110/OsGELP115 catalyze different compounds for pollen exine development.

Lectin receptor kinase OsLecRK-S.7 is required for pollen development and male fertility.

Pollen grains are covered by exine that protects the pollen from stress and facilitates pollination. Here we isolated a male sterile mutant s13283 in rice exhibiting aborted pollen with abnormal exine and defective aperture. The mutant gene encodes a novel plasma membrane-localized legume-lectin receptor kinase that we named OsLecRK-S.7. OsLecRK-S.7 was expressed at different levels in all tested tissues and throughout anther development. In vitro kinase assay showed OsLecRK-S.7 capable of autophosporylation. Mutation in s13283 (E560K) and mutation of the conserved ATP binding site (K418E) both knocked out the kinase activity. Mass spectrometry showed Thr376 , Ser378 , Thr386 , Thr403 , and Thr657 to be the autophosphorylation sites. Mutation of individual autophosphorylation site affected the in vitro kinase activity to different degrees, but did not abolish the gene function in fertility complementation. oslecrk-s.7 mutant plant overexpressing OsLecRK-S.7 recovered male fertility but showed severe growth retardation with reduced number of tillers, and these phenotypes were abolished by E560K or K418E mutation. The results indicated that OsLecRK-S.7 was a key regulator of pollen development.

Increased Interleukin-11 Levels Are Correlated with Cardiac Events in Patients with Chronic Heart Failure.

BACKGROUND: Interleukin-11 (IL-11) is an important inflammatory cytokine and has been demonstrated to participate in cardiovascular diseases. However, there have been no studies about the role of IL-11 in heart failure (HF). The present study is aimed at investigating whether IL-11 levels are associated with the cardiac prognosis in patients with HF. METHODS: The plasma concentrations of IL-11 were measured in 240 patients with chronic HF (CHF) and 80 control subjects without signs of significant heart disease. In addition, we prospectively followed these CHF patients to endpoints of cardiac events. RESULTS: Compared with the control group, the plasma IL-11 concentrations were significantly increased in the CHF patients and gradually increased in the New York Heart Association (NYHA) functional class II group, the NYHA functional class III group, and the NYHA functional class IV group. The receiver operating characteristic (ROC) curve revealed that the predictive role of IL-11 in HF is not as good as N-terminal B-type natriuretic peptide (BNP), although IL-11 has a certain value in predicting cardiac events. In addition, the CHF patients were divided into 3 groups according to the plasma IL-11 concentration category (low, T1; middle, T2; and high, T3). The multivariate Cox hazard analysis showed that the high plasma IL-11 concentrations were independently associated with the presence of cardiac events after adjustment for confounding factors. Furthermore, the CHF patients were divided into two groups based on the median plasma IL-11 concentrations. The Kaplan-Meier analysis revealed that the patients with high IL-11 concentrations had a higher risk of cardiac events compared with those with low IL-11 concentrations. CONCLUSIONS: Higher plasma IL-11 levels significantly increase the presence of cardiac events and suggest a poor outcome; although the diagnostic value of IL-11 in CHF is not as good as BNP, there is a certain value in predicting cardiac events in CHF.

Thioredoxin and NADPH-Dependent Thioredoxin Reductase C Regulation of Tetrapyrrole Biosynthesis.

In chloroplasts, thioredoxin (TRX) isoforms and NADPH-dependent thioredoxin reductase C (NTRC) act as redox regulatory factors involved in multiple plastid biogenesis and metabolic processes. To date, less is known about the functional coordination between TRXs and NTRC in chlorophyll biosynthesis. In this study, we aimed to explore the potential functions of TRX m and NTRC in the regulation of the tetrapyrrole biosynthesis (TBS) pathway. Silencing of three genes, TRX m1, TRX m2, and TRX m4 (TRX ms), led to pale-green leaves, a significantly reduced 5-aminolevulinic acid (ALA)-synthesizing capacity, and reduced accumulation of chlorophyll and its metabolic intermediates in Arabidopsis (Arabidopsis thaliana). The contents of ALA dehydratase, protoporphyrinogen IX oxidase, the I subunit of Mg-chelatase, Mg-protoporphyrin IX methyltransferase (CHLM), and NADPH-protochlorophyllide oxidoreductase were decreased in triple TRX m-silenced seedlings compared with the wild type, although the transcript levels of the corresponding genes were not altered significantly. Protein-protein interaction analyses revealed a physical interaction between the TRX m isoforms and CHLM. 4-Acetoamido-4-maleimidylstilbene-2,2-disulfonate labeling showed the regulatory impact of TRX ms on the CHLM redox status. Since CHLM also is regulated by NTRC (Richter et al., 2013), we assessed the concurrent functions of TRX m and NTRC in the control of CHLM. Combined deficiencies of three TRX m isoforms and NTRC led to a cumulative decrease in leaf pigmentation, TBS intermediate contents, ALA synthesis rate, and CHLM activity. We discuss the coordinated roles of TRX m and NTRC in the redox control of CHLM stability with its corollary activity in the TBS pathway.

M-type thioredoxins are involved in the xanthophyll cycle and proton motive force to alter NPQ under low-light conditions in Arabidopsis.

KEY MESSAGE: M-type thioredoxins are required to regulate zeaxanthin epoxidase activity and to maintain the steady-state level of the proton motive force, thereby influencing NPQ properties under low-light conditions in Arabidopsis. Non-photochemical quenching (NPQ) helps protect photosynthetic organisms from photooxidative damage via the non-radiative dissipation of energy as heat. Energy-dependent quenching (qE) is a major constituent of NPQ. However, the mechanism underlying the regulation of qE is not well understood. In this study, we demonstrate that the m-type thioredoxins TRX-m1, TRX-m2, and TRX-m4 (TRX-ms) interact with the xanthophyll cycle enzyme zeaxanthin epoxidase (ZE) and are required for maintaining the redox-dependent stabilization of ZE by regulating its intermolecular disulfide bridges. Reduced ZE activity and accumulated zeaxanthin levels were observed under TRX-ms deficiency. Furthermore, concurrent deficiency of TRX-ms resulted in a significant increase in proton motive force (pmf) and acidification of the thylakoid lumen under low irradiance, perhaps due to the significantly reduced ATP synthase activity under TRX-ms deficiency. The increased pmf, combined with acidification of the thylakoid lumen and the accumulation of zeaxanthin, ultimately contribute to the elevated stable qE in VIGS-TRX-m2m4/m1 plants under low-light conditions. Taken together, these results indicate that TRX-ms are involved in regulating NPQ-dependent photoprotection in Arabidopsis.

Erratum to "Anti-Interleukin-22-Neutralizing Antibody Attenuates Angiotensin II-Induced Cardiac Hypertrophy in Mice".

[This corrects the article DOI: 10.1155/2017/5635929.].