The Mevalonate Pathway Is Important for Growth, Spore Production, and the Virulence of Phytophthora sojae

The mevalonate (MVA) pathway in eukaryotic organisms produces isoprenoids, sterols, ubiquinone, and dolichols. These molecules are vital for diverse cellular functions, ranging from signaling to membrane integrity, and from post-translational modification to energy homeostasis. However, information on the MVA pathway in Phytophthora species is limited. In this study, we identified the MVA pathway genes and reconstructed the complete pathway in Phytophthora sojae in silico. We characterized the function of the MVA pathway of P. sojae by treatment with enzyme inhibitor lovastatin, deletion of the geranylgeranyl diphosphate synthase gene (PsBTS1), and transcriptome profiling analysis. The MVA pathway is ubiquitously conserved in Phytophthora species. Under lovastatin treatment, mycelial growth, spore production, and virulence of P. sojae were inhibited but the zoospore encystment rate increased. Heterozygous mutants of PsBTS1 showed slow growth, abnormal colony characteristics, and mycelial morphology. Mutants showed decreased numbers of sporangia and oospores as well as reduced virulence. RNA sequencing analysis identified the essential genes in sporangia formation were influenced by the enzyme inhibitor lovastatin. Our findings elucidate the role of the MVA pathway in P. sojae and provide new insights into the molecular mechanisms underlying the development, reproduction, and virulence of P. sojae and possibly other oomycetes. Our results also provide potential chemical targets for management of plant Phytophthora diseases.

Download Full-text

Changes on proteomic and metabolomic profile in serum of mice induced by chronic exposure to tramadol

Scientific Reports ◽

10.1038/s41598-021-81109-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Shukun Jiang ◽

Guojie Liu ◽

Huiya Yuan ◽

Enyu Xu ◽

Wei Xia ◽

...

Keyword(s):

Chronic Exposure ◽

Molecular Mechanisms ◽

Fatty Acid Biosynthesis ◽

Serum Proteins ◽

Enzyme Inhibitor ◽

Bile Secretion ◽

Control Group ◽

Protein Digestion ◽

Metabolomic Profile ◽

Apolipoprotein C

AbstractTramadol is an opioid used as an analgesic for treating moderate or severe pain. The long-term use of tramadol can induce several adverse effects. The toxicological mechanism of tramadol abuse is unclear. Limited literature available indicates the change of proteomic profile after chronic exposure to tramadol. In this study, we analyzed the proteomic and metabolomic profile by TMT-labeled quantitative proteomics and untargeted metabolomics between the tramadol and the control group. Proteomic analysis revealed 31 differential expressed serum proteins (9 increased and 22 decreased) in tramadol-treated mice (oral, 50 mg/kg, 5 weeks) as compared with the control ones. Bioinformatics analysis showed that the dysregulated proteins mainly included: enzyme inhibitor-associated proteins (i.e. apolipoprotein C-III (Apoc-III), alpha-1-antitrypsin 1–2 (Serpina 1b), apolipoprotein C-II (Apoc-II), plasma protease C1 inhibitor, inter-alpha-trypsin inhibitor heavy chain H3 (itih3)); mitochondria-related proteins (i.e. 14-3-3 protein zeta/delta (YWHAZ)); cytoskeleton proteins (i.e. tubulin alpha-4A chain (TUBA4A), vinculin (Vcl)). And we found that the differential expressed proteins mainly involved in the pathway of the protein digestion and absorption. Metabolomics analysis revealed that differential expressed metabolites mainly involved in protein ingestion and absorption, fatty acid biosynthesis, steroid hormone biosynthesis and bile secretion. Our overall findings revealed that chronic exposure to tramadol changed the proteomic and metabolomic profile of mice. Moreover, integrated proteomic and metabolomic revealed that the protein digestion and absorption is the common enrichment KEGG pathway. Thus, the combination of proteomics and metabolomics opens new avenues for the research of the molecular mechanisms of tramadol toxicity.

Download Full-text

MicroRNAs from Snellenius manilae bracovirus regulate innate and cellular immune responses of its host Spodoptera litura

Communications Biology ◽

10.1038/s42003-020-01563-3 ◽

2021 ◽

Vol 4 (1) ◽

Author(s):

Cheng-Kang Tang ◽

Chih-Hsuan Tsai ◽

Carol-P. Wu ◽

Yu-Hsien Lin ◽

Sung-Chan Wei ◽

...

Keyword(s):

Immune Responses ◽

Spodoptera Litura ◽

Molecular Mechanisms ◽

Innate Immune ◽

Sequencing Analysis ◽

Innate Immune Responses ◽

Cellular Immune Responses ◽

Next Generation Sequencing Analysis ◽

Cellular Immune ◽

Generation Sequencing

AbstractTo avoid inducing immune and physiological responses in insect hosts, parasitoid wasps have developed several mechanisms to inhibit them during parasitism, including the production of venom, specialized wasp cells, and symbioses with polydnaviruses (PDVs). These mechanisms alter the host physiology to give the wasp offspring a greater chance of survival. However, the molecular mechanisms for most of these alterations remain unclear. In the present study, we applied next-generation sequencing analysis and identified several miRNAs that were encoded in the genome of Snellenius manilae bracovirus (SmBV), and expressed in the host larvae, Spodoptera litura, during parasitism. Among these miRNAs, SmBV-miR-199b-5p and SmBV-miR-2989 were found to target domeless and toll-7 in the host, which are involved in the host innate immune responses. Microinjecting the inhibitors of these two miRNAs into parasitized S. litura larvae not only severely decreased the pupation rate of Snellenius manilae, but also restored the phagocytosis and encapsulation activity of the hemocytes. The results demonstrate that these two SmBV-encoded miRNAs play an important role in suppressing the immune responses of parasitized hosts. Overall, our study uncovers the functions of two SmBV-encoded miRNAs in regulating the host innate immune responses upon wasp parasitism.

Download Full-text

Transcriptome Analysis Reveals the Genes Involved in Bifidobacterium Longum FGSZY16M3 Biofilm Formation

Microorganisms ◽

10.3390/microorganisms9020385 ◽

2021 ◽

Vol 9 (2) ◽

pp. 385 ◽

Cited By ~ 1

Author(s):

Zongmin Liu ◽

Lingzhi Li ◽

Qianwen Wang ◽

Faizan Ahmed Sadiq ◽

Yuankun Lee ◽

...

Keyword(s):

Network Analysis ◽

Biofilm Formation ◽

Extracellular Polymeric Substances ◽

Molecular Mechanisms ◽

Early Stage ◽

Bifidobacterium Longum ◽

Regulation Of Gene Expression ◽

Interaction Network ◽

Structural Development ◽

Sequencing Analysis

Biofilm formation has evolved as an adaptive strategy for bacteria to cope with harsh environmental conditions. Currently, little is known about the molecular mechanisms of biofilm formation in bifidobacteria. A time series transcriptome sequencing analysis of both biofilm and planktonic cells of Bifidobacterium longum FGSZY16M3 was performed to identify candidate genes involved in biofilm formation. Protein–protein interaction network analysis of 1296 differentially expressed genes during biofilm formation yielded 15 clusters of highly interconnected nodes, indicating that genes related to the SOS response (dnaK, groS, guaB, ruvA, recA, radA, recN, recF, pstA, and sufD) associated with the early stage of biofilm formation. Genes involved in extracellular polymeric substances were upregulated (epsH, epsK, efp, frr, pheT, rfbA, rfbJ, rfbP, rpmF, secY and yidC) in the stage of biofilm maturation. To further investigate the genes related to biofilm formation, weighted gene co-expression network analysis (WGCNA) was performed with 2032 transcript genes, leading to the identification of nine WGCNA modules and 133 genes associated with response to stress, regulation of gene expression, quorum sensing, and two-component system. These results indicate that biofilm formation in B. longum is a multifactorial process, involving stress response, structural development, and regulatory processes.

Download Full-text

Feedback Regulation of O-GlcNAc Transferase through Translation Control to Maintain Intracellular O-GlcNAc Homeostasis

International Journal of Molecular Sciences ◽

10.3390/ijms22073463 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3463

Author(s):

Chia-Hung Lin ◽

Chen-Chung Liao ◽

Mei-Yu Chen ◽

Teh-Ying Chou

Keyword(s):

Molecular Mechanisms ◽

Mrna Level ◽

Feedback Regulation ◽

Translation Initiation Factor ◽

Initiation Factor ◽

Cell Physiology ◽

Hydroxyl Groups ◽

Post Translational Modification ◽

Translation Control ◽

Glcnac Transferase

Protein O-GlcNAcylation is a dynamic post-translational modification involving the attachment of N-acetylglucosamine (GlcNAc) to the hydroxyl groups of Ser/Thr residues on numerous nucleocytoplasmic proteins. Two enzymes are responsible for O-GlcNAc cycling on substrate proteins: O-GlcNAc transferase (OGT) catalyzes the addition while O-GlcNAcase (OGA) helps the removal of GlcNAc. O-GlcNAcylation modifies protein functions; therefore, dysregulation of O-GlcNAcylation affects cell physiology and contributes to pathogenesis. To maintain homeostasis of cellular O-GlcNAcylation, there exists feedback regulation of OGT and OGA expression responding to fluctuations of O-GlcNAc levels; yet, little is known about the molecular mechanisms involved. In this study, we investigated the O-GlcNAc-feedback regulation of OGT and OGA expression in lung cancer cells. Results suggest that, upon alterations in O-GlcNAcylation, the regulation of OGA expression occurs at the mRNA level and likely involves epigenetic mechanisms, while modulation of OGT expression is through translation control. Further analyses revealed that the eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) contributes to the downregulation of OGT induced by hyper-O-GlcNAcylation; the S5A/S6A O-GlcNAcylation-site mutant of 4E-BP1 cannot support this regulation, suggesting an important role of O-GlcNAcylation. The results provide additional insight into the molecular mechanisms through which cells may fine-tune intracellular O-GlcNAc levels to maintain homeostasis.

Download Full-text

mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth

The Journal of Cell Biology ◽

10.1083/jcb.202102122 ◽

2021 ◽

Vol 220 (11) ◽

Author(s):

Jingjing Zhang ◽

Ying Hu ◽

Yanli Wang ◽

Lin Fu ◽

Xiumei Xu ◽

...

Keyword(s):

Energy Homeostasis ◽

Membrane Integrity ◽

Lipid Synthesis ◽

Droplet Growth ◽

Side Chain ◽

C Elegans ◽

Branched Chain Fatty Acids ◽

Intracellular Organelles ◽

Branched Chain ◽

Er Homeostasis

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.

Download Full-text

Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions

Acta Endocrinologica ◽

10.1530/eje.0.1490079 ◽

2003 ◽

Vol 149 (2) ◽

pp. 79-90 ◽

Cited By ~ 160

Author(s):

ML Raffin-Sanson ◽

Y de Keyzer ◽

X Bertagna

Keyword(s):

Anterior Pituitary ◽

Energy Homeostasis ◽

Molecular Mechanisms ◽

Single Gene ◽

Local Production ◽

Biological Functions ◽

Multiple Functions ◽

Pathological Conditions ◽

Recent Developments ◽

The Brain

Proopiomelanocortin (POMC) is the polypeptide precursor of ACTH. First discovered in anterior pituitary corticotroph cells, it has more recently been revealed to have many other physiological aspects. The fine molecular mechanisms of ACTH biosynthesis show that ACTH is but one piece of a puzzle which contains many other peptides. Present in various tIssues, among which are pituitary, hypothalamus, central nervous system and skin, POMC undergoes extensive post-translational processing. This processing is tIssue-specific and generates, depending on the case, various sets of peptides involved in completely diverse biological functions. POMC expressed in corticotroph cells of the pituitary is necessary for adrenal function. Recent developments have shown that POMC-expressing neurons in the brain play a major role in the control of pain and energy homeostasis. Local production of POMC-derived peptides in skin may influence melanogenesis. A still unknown function in the placenta is likely.POMC has become a paradigmatic polypeptide precursor model illustrating the variable roles of a single gene and its various products in different localities.

Download Full-text

The Impact of Medium Chain and Polyunsaturated ω-3-Fatty Acids on Amyloid-β Deposition, Oxidative Stress and Metabolic Dysfunction Associated with Alzheimer´s Disease

Antioxidants ◽

10.3390/antiox10121991 ◽

2021 ◽

Vol 10 (12) ◽

pp. 1991

Author(s):

Janine Mett

Keyword(s):

Oxidative Stress ◽

Fatty Acids ◽

Energy Metabolism ◽

Molecular Mechanisms ◽

Current Knowledge ◽

Membrane Integrity ◽

Amyloid Β ◽

The Elderly ◽

Medium Chain ◽

The Impact

Alzheimer’s disease (AD), the most common cause of dementia in the elderly population, is closely linked to a dysregulated cerebral lipid homeostasis and particular changes in brain fatty acid (FA) composition. The abnormal extracellular accumulation and deposition of the peptide amyloid-β (Aβ) is considered as an early toxic event in AD pathogenesis, which initiates a series of events leading to neuronal dysfunction and death. These include the induction of neuroinflammation and oxidative stress, the disruption of calcium homeostasis and membrane integrity, an impairment of cerebral energy metabolism, as well as synaptic and mitochondrial dysfunction. Dietary medium chain fatty acids (MCFAs) and polyunsaturated ω-3-fatty acids (ω-3-PUFAs) seem to be valuable for disease modification. Both classes of FAs have neuronal health-promoting and cognition-enhancing properties and might be of benefit for patients suffering from mild cognitive impairment (MCI) and AD. This review summarizes the current knowledge about the molecular mechanisms by which MCFAs and ω-3-PUFAs reduce the cerebral Aβ deposition, improve brain energy metabolism, and lessen oxidative stress levels.

Download Full-text

Studies on trans-sutural distraction osteogenesis-related genes based on transcriptome sequencing

10.1101/2020.04.11.037085 ◽

2020 ◽

Author(s):

Baicheng Wang ◽

Hongyu Xue ◽

Haizhou Tong ◽

Peiyang Zhang ◽

Mei Wang ◽

...

Keyword(s):

Cell Cycle ◽

Distraction Osteogenesis ◽

Transcriptome Sequencing ◽

Molecular Mechanisms ◽

Sequencing Analysis ◽

Sprague Dawley ◽

Down Regulation ◽

Important Approach ◽

Immune Pathways ◽

Experimental Group

AbstractTrans-sutural distraction osteogenesis (TSDO) is an important approach to improve mid-face hypoplasia. In recent years, many studies have been carried out on physical mechanisms of TSDO; however, it’s specific cytological and molecular mechanisms are still unclear. In this study, we performed transcriptome sequencing analysis in Sprague Dawley rats at 1 and 2 weeks after suture osteogenesis and compared RNA expression levels between experimental and control groups. At one week, enrichment pathways were mainly up-regulated in muscle- and bone-related pathways. By contrast, pathways of the immune system showed a state of inhibition and down-regulation, especially for B cells; the main immune pathways showed significant down-regulation. However, two weeks later, the experimental group showed positive up-regulation of the pathways related to DNA synthesis and replication, cell cycle, and chromosome replication. At the same time, the immune pathways that were down-regulated in the first week were up-regulated in the second week. In other words, the up-regulated muscle- and bone-related pathways show opposite trends. The expression of bone- and myogenesis-related transcriptome was up-regulated and the immune-related pathways were down-regulated in the experimental group at 1 week. At 2 weeks, the pathways related to bone- and muscle were down-regulated, while those related to cell cycle regulation and DNA replication were up-regulated. These results suggest that musculoskeletal-related molecules may play an important role during suture osteogenesis at 1 week, and immune regulation may be involved in this process; however, at 2 weeks, molecules related to cell proliferation and replication may be a major role.

Download Full-text

Comparative phosphoproteome analysis to identify candidate phosphoproteins involved in blue light-induced brown film formation in Lentinula edodes

PeerJ ◽

10.7717/peerj.9859 ◽

2020 ◽

Vol 8 ◽

pp. e9859

Author(s):

Tingting Song ◽

Yingyue Shen ◽

Qunli Jin ◽

Weilin Feng ◽

Lijun Fan ◽

...

Keyword(s):

Blue Light ◽

Molecular Mechanisms ◽

Lentinula Edodes ◽

Film Formation ◽

Quantitative Information ◽

Light Signal ◽

Post Translational Modification ◽

Bioinformatics Analyses ◽

Phosphorylated Proteins ◽

Liquid Chromatography Tandem Mass

Light plays an important role in the growth and differentiation of Lentinula edodes mycelia, and mycelial morphology is influenced by light wavelengths. The blue light-induced formation of brown film on the vegetative mycelial tissues of L. edodes is an important process. However, the mechanisms of L. edodes’ brown film formation, as induced by blue light, are still unclear. Using a high-resolution liquid chromatography-tandem mass spectrometry integrated with a highly sensitive immune-affinity antibody method, phosphoproteomes of L. edodes mycelia under red- and blue-light conditions were analyzed. A total of 11,224 phosphorylation sites were identified on 2,786 proteins, of which 9,243 sites on 2,579 proteins contained quantitative information. In total, 475 sites were up-regulated and 349 sites were down-regulated in the blue vs red group. To characterize the differentially phosphorylated proteins, systematic bioinformatics analyses, including gene ontology annotations, domain annotations, subcellular localizations, and Kyoto Encyclopedia of Genes and Genomes pathway annotations, were performed. These differentially phosphorylated proteins were correlated with light signal transduction, cell wall degradation, and melanogenesis, suggesting that these processes are involved in the formation of the brown film. Our study provides new insights into the molecular mechanisms of the blue light-induced brown film formation at the post-translational modification level.

Download Full-text

Relationship between mitochondrial changes and seed aging as a limitation of viability for the storage of beech seed (Fagus sylvatica L.)

PeerJ ◽

10.7717/peerj.10569 ◽

2021 ◽

Vol 9 ◽

pp. e10569

Author(s):

Arleta Małecka ◽

Liliana Ciszewska ◽

Aleksandra Staszak ◽

Ewelina Ratajczak

Keyword(s):

Fagus Sylvatica ◽

Molecular Mechanisms ◽

Membrane Integrity ◽

Natural Aging ◽

Seed Storage ◽

Biological Processes ◽

Embryonic Axes ◽

Seed Aging ◽

Fagus Sylvatica L

Aging is one of the most fundamental biological processes occurring in all forms of eukaryotic life. Beech trees (Fagus sylvatica L.) produce seeds in intervals of 5–10 years. Its yearly seed yield is usually very low, so there is a need for long-term seed storage to enable propagation of this species upon demand. Seeds for sowing must be of high quality but they are not easy to store without viability loss. Understanding the mechanism responsible for seed aging is therefore very important. We observed the generation of reactive oxygen species (ROS) in mitochondria of embryonic axes and cotyledons of beech seeds during natural aging. The presence of ROS led to changes in compromised mitochondrial membrane integrity and in mitochondrial metabolism and morphology. In this study, we pointed to the involvement of mitochondria in the natural aging process of beech seeds, but the molecular mechanisms underlying this involvement are still unknown.

Download Full-text