Arabidopsis plasma membrane H+-ATPase interacts with auxin to regulate Danger-Associated Peptide Pep1-induced root growth inhibition.

Plant elicitor peptide 1 (Pep1) is one of plant-derived damage-associated molecular patterns (DAMPs) involved in the regulation of multiple biological processes, including immune response and root growth. The exogenous application of Pep1 was shown to inhibit root growth by affecting the auxin content and extracellular pH level in the transition zone (TZ). However, the signaling relationship between extracellular pH and auxin in Pep1-regulated root growth inhibition has not been explored. Our study here suggested that both pH signaling and auxin signaling were responsible for Pep1-regulated root growth inhibition, and the Pep1-induced auxin accumulation in TZ depended on apoplastic acidification. To increase the apoplastic pH in TZ, we mutated the AHA2 and found that the mutants of aha2-4 and pin2aha2-4 both reduced Pep1-induced auxin content in TZ, thereby alleviating root growth inhibition. Thus, our results reveal a new auxin-pH signaling crosstalk mechanism in regulating root growth, and provide new insights into the function of Pep1 in regulating root growth in Arabidopsis.

Danger-Associated Peptides Interact with PIN-Dependent Local Auxin Distribution to Inhibit Root Growth in Arabidopsis.

Plant elicitor peptides (Peps) are damage/danger-associated molecular patterns that are perceived by the receptor-like kinases, PEPR1 and PEPR2, to enhance innate immunity and to inhibit root growth in Arabidopsis (Arabidopsis thaliana). Here, we show that Arabidopsis Pep1 inhibits root growth in a PEPR2-dependent manner, which is accompanied by swelling epidermal and cortex cells and root hair formation in the transition zone (TZ). These Pep1-induced changes were mimicked by exogenous auxin application and were suppressed in the auxin perception mutants transport inhibitor response1 (tir1) and tir1 afb1 afb2 Pep1-induced auxin accumulation in the TZ region preceded cell expansion in roots. Because local auxin distribution depends on PIN-type auxin transporters, we examined Pep1-PEPR-induced root growth inhibition in several pin mutants and found that pin2 was highly sensitive but pin3 was less sensitive to Pep1. The pin2 pin3 double mutant was as sensitive to Pep1 treatment as wild-type plants. Pep1 reduced the abundance of PIN2 in the plasma membrane through activating endocytosis while increasing PIN3 expression in the TZ, leading to changes in local auxin distribution and inhibiting root growth. These results suggest that Pep-PEPR signaling undergoes crosstalk with auxin accumulation to control cell expansion and differentiation in roots during immune responses.

Polysaccharide CM1 from Cordyceps militaris hinders adipocyte differentiation and alleviates hyperlipidemia in LDLR(+/-) hamsters.

BACKGROUND: Cordyceps militaris is cultured widely as an edible mushroom and accumulating evidence in mice have demonstrated that the polysaccharides of Cordyceps species have lipid-lowering effects. However, lipid metabolism in mice is significantly different from that in humans, making a full understanding of the mechanisms at play critical. METHODS: After 5 months, the hamsters were weighed and sampled under anesthesia after overnight fasting. The lipid-lowering effect and mechanisms of the polysaccharide CM1 was investigated by cellular and molecular technologies. Furthermore, the effect of the polysaccharide CM1 (100 µg/mL) on inhibiting adipocyte differentiation was investigated in vitro. RESULTS: CM1, a polysaccharide from C. militaris, significantly decreased plasma total cholesterol, triglyceride and epididymal fat index in LDLR(+/-) hamsters, which have a human-like lipid profile. After 5 months' administration, CM1 decreased the plasma level of apolipoprotein B48, modulated the expression of key genes and proteins in liver, small intestine, and epididymal fat. CM1 also inhibited preadipocyte differentiation in 3T3-L1 cells by downregulating the key genes involved in lipid droplet formation. CONCLUSIONS: The polysaccharide CM1 lowers lipid and adipocyte differentiation by several pathways, and it has potential applications for hyperlipidemia prevention.

Transcription Factor WRKY33 Mediates the Phosphate Deficiency-Induced Remodeling of Root Architecture by Modulating Iron Homeostasis in Arabidopsis Roots.

The remodeling of root architecture is regarded as a major development to improve the plant's adaptivity to phosphate (Pi)-deficient conditions. The WRKY transcription factors family has been reported to regulate the Pi-deficiency-induced systemic responses by affecting Pi absorption or transportation. Whether these transcription factors act as a regulator to mediate the Pi-deficiency-induced remodeling of root architecture, a typical local response, is still unclear. Here, we identified an Arabidopsis transcription factor, WRKY33, that acted as a negative regulator to mediate the Pi-deficiency-induced remodeling of root architecture. The disruption of WRKY33 in wrky33-2 mutant increased the plant's low Pi sensitivity by further inhibiting the primary root growth and promoting the formation of root hair. Furthermore, we revealed that WRKY33 negatively regulated the remodeling of root architecture by controlling the transcriptional expression of ALMT1 under Pi-deficient conditions, which further mediated the Fe3+ accumulation in root tips to inhibit the root growth. In conclusion, this study demonstrates a previously unrecognized signaling crosstalk between WRKY33 and the ALMT1-mediated malate transport system to regulate the Pi deficiency responses.

Danger-Associated Peptide Regulates Root Growth by Promoting Protons Extrusion in an AHA2-Dependent Manner in Arabidopsis.

Plant elicitor peptides (Peps) are damage/danger-associated molecular patterns (DAMPs) that are derived from precursor proteins PROPEPs and perceived by a pair of leucine-rich repeat receptor-like kinases (LRR-RLKs), PEPR1 and PEPR2, to enhance innate immunity and to inhibit root growth in Arabidopsis thaliana. In this study, we show that Arabidopsis Pep1 inhibits the root growth by interfering with pH signaling, as acidic condition increased, but neutral and alkaline conditions decreased the Pep1 effect on inhibiting the root growth. The perception of Pep1 to PEPRs activated the plasma membrane-localized H+-ATPases (PM H+-ATPases) -the pump proton in plant cell-to extrude the protons into apoplast, and induced an overly acidic environment in apoplastic space, which further promoted the cell swelling in root apex and inhibited root growth. Furthermore, we revealed that pump proton AUTOINHIBITED H+-ATPase 2 (AHA2) physically interacted with PEPR2 and served downstream of the Pep1-PEPRs signaling pathway to regulate Pep1-induced protons extrusion and root growth inhibition. In conclusion, this study demonstrates a previously unrecognized signaling crosstalk between Pep1 and pH signaling to regulate root growth.

Danger-Associated Peptide Regulates Root Immune Responses and Root Growth by Affecting ROS Formation in Arabidopsis.

Plant elicitor peptides (Peps) are damage/danger-associated molecular patterns (DAMPs) that are perceived by a pair of receptor-like kinases, PEPR1 and PEPR2, to enhance innate immunity and induce the growth inhibition of root in Arabidopsis thaliana. In this study, we show that PEPR1 and PEPR2 function vitally in roots to regulate the root immune responses when treating the roots with bacterial pathogen Pst DC3000. PEPR2, rather than PEPR1, played a predominant role in the perception of Pep1 in the roots and further triggered a strong ROS accumulation-the substance acts as an antimicrobial agent or as a secondary messenger in plant cells. Consistently, seedlings mutating two major ROS-generating enzyme genes, respiratory burst oxidase homologs D and F (RBOHD and RBOHF), abolished the root ROS accumulation and impaired the growth inhibition of the roots induced by Pep1. Furthermore, we revealed that botrytis-induced kinase 1 (BIK1) physically interacted with PEPRs and RBOHD/F, respectively, and served downstream of the Pep1-PEPRs signaling pathway to regulate Pep1-induced ROS production and root growth inhibition. In conclusion, this study demonstrates a previously unrecognized signaling crosstalk between Pep1 and ROS signaling to regulate root immune response and root growth.

Sea cucumber-derived compounds for treatment of dyslipidemia: A review.

Dyslipidemias are disorders of plasma levels of lipids, such as elevated levels of total cholesterol and triglyceride, that are associated with various human diseases including cardiovascular disease (CVD) and non-alcoholic fatty liver disease (NAFLD). Statins are the first-line drugs for treatment of dyslipidemia. However, a substantial proportion of patients cannot reach the recommended LDL-c level even with the highest tolerated doses of statins, and there is no available drug specifically for NAFLD therapy. Sea cucumbers are one of the widely distributed invertebrates, and are an important resource of food and medicine. Sea cucumbers have many valuable nutrients including saponins, fatty acids, phospholipids, cerebrosides, sulfated polysaccharides, as well as proteins and peptides. In recent years, these natural products derived from sea cucumbers have attracted attentions for treatment of CVD and NAFLD because of their lipid-lowering effect and low toxicity. However, the hypolipidemic mechanisms of action and the structure-activity relationship of these bioactive components have not been well-documented in literature. This review article summarizes the signaling pathways and the potential structure-activity relationship of sea cucumber-derived bioactive compounds including saponins, lipids, carbohydrates as well as peptides and proteins. This article will provide information useful for the development of sea cucumber-derived lipid-lowering compounds as well as for investigation of hypolipidemic compounds that are derived from other natural resources.

The polysaccharide-peptide complex from mushroom Cordyceps militaris ameliorates atherosclerosis by modulating the lncRNA-miRNA-mRNA axis.

An N-glycosidic polysaccharide-peptide complex CMPS-80 was obtained from the fruiting body of C. militaris. Of importance, CMPS-80 significantly ameliorated formation of atherosclerotic lesions and plasma lipid profiles in apolipoprotein E-deficient mice. Integrated informatics analysis suggested that CMPS-80 can modulate multiple lncRNA-microRNA-mRNA axes. CMPS-80 has a potential application for prevention of hyperlipidemia and atherosclerosis.

Integrated bioinformatics analysis of the anti-atherosclerotic mechanisms of the polysaccharide CM1 from Cordyceps militaris.

Cordyceps militaris is a well-known traditional Chinese medicine. Studies have demonstrated that the polysaccharides of C. militaris have various bioactivities. However, their mechanisms of action remain unclear. We previously purified a water-soluble polysaccharide CM1 from C. militaris and found that it has a cholesterol efflux improving capacity. This study further investigates the effect of CM1 in anti-atherosclerosis and its underlying mechanism in apolipoprotein E-deficient mice. Our data indicated that CM1 significantly decreased the total cholesterol and triglyceride in the plasma of mice, and decreased lipid deposition and formation of atherosclerotic plaque in a dose-dependent manner. Integrated bioinformatics analysis revealed that CM1 interacted with multiple signaling pathways, including those involved in lipid metabolism, inflammatory response, oxidoreductase activity and fluid shear stress, to exert its anti-atherosclerotic effect. Molecular technology analysis showed that CM1 enhanced the expression of proteins involved in lipid metabolism, reduced the expression of intercellular adhesion molecule-1 and tumor necrosis factor-α in the aorta, and decreased the content of oxidative products by enhancing the activities of antioxidant enzymes. Microarray analysis and biochemical data indicated that CM1 can improve lipid metabolism, reduce inflammation and oxidative stress. Taken together, CM1 could be used for the treatment of hyperlipidemia and atherosclerotic cardiovascular diseases.

The Cordyceps militaris-Derived Polysaccharide CM1 Alleviates Atherosclerosis in LDLR(-/-) Mice by Improving Hyperlipidemia.

Atherosclerotic cardiovascular disease has a high mortality worldwide. Our lab previously purified a polysaccharide designated as CM1 with (1→4)-ß-D-Glcp and (1→2)-α-D-Manp glycosyls as the backbone. In this study, we investigated the anti-atherosclerosis effect of CM1 and the underlying mechanisms of action in a low-density lipoprotein receptor knockout (LDLR(-/-) mouse model. It was found that CM1 significantly decreased the formation of atherosclerotic plaques. Mechanistically, CM1 enhanced plasma level of apolipoprotein A-I and decreased the plasma levels of triglyceride, apolipoprotein B, and total cholesterol. In the absence of LDLR, CM1 elevated the expression of very low-density lipoprotein receptor for liver uptake of plasma apolipoprotein B-containing particles and reduced hepatic triglyceride synthesis by inhibiting sterol regulatory element binding protein 1c. CM1 improved lipids excretion by increasing the liver X receptor α/ATP-binding cassette G5 pathway in small intestine. CM1 reduced lipogenesis and lipolysis by inhibiting peroxisome proliferator-activated receptor γ and adipose triglyceride lipase in epididymal fat. Furthermore, CM1 improved lipid profile in C57BL/6J mice. Collectively, CM1 can modulate lipid metabolism by multiple pathways, contributing to reduced plasma lipid level and formation of atherosclerotic plaques in LDLR(-/-) mice. This molecule could be explored as a potential compound for prevention and treatment of hyperlipidemia and atherosclerosis.

Purification, characterization and anti-atherosclerotic effects of the polysaccharides from the fruiting body of Cordyceps militaris.

Hyperlipidemia is one major cause of atherosclerosis, which is a basic pathological change of cardiovascular diseases. Polysaccharide is a water-soluble component with lipid-lowering effects. In this study, alkaline-extracted polysaccharides were obtained from the fruiting body of C. militaris. Polysaccharides were purified via anion exchange and size exclusion chromatography. Their structural characteristics were investigated via chemical and spectroscopic methods. CM3I was mainly composed of →4)α-D-Glcp(1 → glycosyls and differed from starch due to the presence of →4,6)ß-D-Glcp(1 → glycosyls. CM3II was characterized by its backbone, which was composed of →4)-ß-D-Manp(1 → 6)-α-D-Manp(1 → 6)-ß-D-Manp(1 → linked glycosyls, and especially the presence of O-methyl. Moreover, CM3II exhibited powerful anti-atherosclerotic effects via lowering plasma lipid levels in apolipoprotein E-deficient mice. The underlying mechanisms were attributed to its promoting effect on LXRα and inhibitory effect on SREBP-2. Collectively, CM3I and CM3II are different from the previously reported polysaccharides from C. militaris, and CM3II has a potential application in hypolipidemia and anti-atherosclerosis.

On optimal backward perturbation analysis for the linear system with skew circulant coefficient matrix.

We first give the style spectral decomposition of a special skew circulant matrix C and then get the style decomposition of arbitrary skew circulant matrix by making use of the Kronecker products between the elements of first row in skew circulant and the special skew circulant C. Besides that, we obtain the singular value of skew circulant matrix as well. Finally, we deal with the optimal backward perturbation analysis for the linear system with skew circulant coefficient matrix on the base of its style spectral decomposition.