Reduction of acetylcholine in the hippocampus of hippocampal cholinergic neurostimulating peptide precursor protein knockout mice

The cholinergic efferent network from the medial septal nucleus to the hippocampus plays an important role in learning and memory processes. This cholinergic projection can generate theta oscillations in the hippocampus to encode novel information. Hippocampal cholinergic neurostimulating peptide (HCNP), which induces acetylcholine (Ach) synthesis in the medial septal nuclei of an explant culture system, was purified from the soluble fraction of postnatal rat hippocampus. HCNP is processed from the N-terminal region of a 186-amino acid, 21-kDa HCNP precursor protein, also known as Raf kinase inhibitory protein and phosphatidylethanolamine-binding protein 1. Here, we confirmed direct reduction of Ach release in the hippocampus of freely moving HCNP-pp knockout mice under an arousal state by the microdialysis method. The levels of vesicular acetylcholine transporter were also decreased in the hippocampus of these mice in comparison with those in control mice, suggesting there was decreased incorporation of Ach into the synaptic vesicle. These results potently indicate that HCNP may be a cholinergic regulator in the septo-hippocampal network.

Overexpression of four MiTFL1 genes from mango delays the flowering time in transgenic Arabidopsis

Background TERMINAL FLOWER 1 (TFL1) belongs to the phosphatidylethanolamine-binding protein (PEBP) family, which is involved in inflorescence meristem development and represses flowering in several plant species. In the present study, four TFL1 genes were cloned from the mango (Mangifera indica L.) variety ‘SiJiMi’ and named MiTFL1-1, MiTFL1-2, MiTFL1-3 and MiTFL1-4. Results Sequence analysis showed that the encoded MiTFL1 proteins contained a conserved PEBP domain and belonged to the TFL1 group. Expression analysis showed that the MiTFL1 genes were expressed in not only vegetative organs but also reproductive organs and that the expression levels were related to floral development. Overexpression of the four MiTFL1 genes delayed flowering in transgenic Arabidopsis. Additionally, MiTFL1-1 and MiTFL1-3 changed the flower morphology in some transgenic plants. Yeast two-hybrid (Y2H) analysis showed that several stress-related proteins interacted with MiTFL1 proteins. Conclusions The four MiTFL1 genes exhibited a similar expression pattern, and overexpression in Arabidopsis resulted in delayed flowering. Additionally, MiTFL1-1 and MiTFL1-3 overexpression affected floral organ development. Furthermore, the MiTFL1 proteins could interact with bHLH and 14-3-3 proteins. These results indicate that the MiTFL1 genes may play an important role in the flowering process in mango.

ScFT6: A Putative Candidate for Sugarcane Floral Inducer

One of the factors that can decrease sugarcane productivity is the flowering, because it affects the quantity and quality of feedstock, due to sucrose consumption from the stem during inflorescence emission. Photoperiodicity is the main environmental factor involved in sugarcane floral induction, which occurs by the integration of gene regulatory networks in response to environmental and endogenous stimuli. One of the genes involved in those regulatory networks is the FLOWERING LOCUS T (FT), which is considered a phloem-mobile signal that stimulates floral induction in the shoot apical meristem. This work aimed to identify and characterize homologs of the FT gene in sugarcane, as well as to determine the putative function of these genes during floral induction. From this perspective, we have conducted in silico analyses of putative FT orthologs in sugarcane, as well as the expression levels in different photoperiodic conditions in a 24-hours-day-cycle of ScFT6 in different plant tissues in contrasting cultivars in terms of flowering time. Three new possible FT orthologs were found with high similarity to FT homologs in other species. Among three genes identified, we highlighted ScFT6, which has a conserved domain and amino acids at characteristic positions for the flowering inducer phosphatidylethanolamine-binding protein gene family. Additionally, its expression occurs according to coincidental model, possibly being controlled by the circadian clock. Cultivars with distinct flowering time behavior display variable expression for the ScFT6 gene, suggesting a possible genotypic relationship for its expression. Therefore, sugarcane has at least one putative orthologous gene in relation to FT that promotes floral induction.

Transcriptional Repression of Raf Kinase Inhibitory Protein Gene by Metadherin during Cancer Progression

Raf kinase inhibitory protein (RKIP), also known as a phosphatidylethanolamine-binding protein 1 (PEBP1), functions as a tumor suppressor and regulates several signaling pathways, including ERK and NF-κκB. RKIP is severely downregulated in human malignant cancers, indicating a functional association with cancer metastasis and poor prognosis. The transcription regulation of RKIP gene in human cancers is not well understood. In this study, we suggested a possible transcription mechanism for the regulation of RKIP in human cancer cells. We found that Metadherin (MTDH) significantly repressed the transcriptional activity of RKIP gene. An analysis of publicly available datasets showed that the knockdown of MTDH in breast and endometrial cancer cell lines induced the expression RKIP. In addition, the results obtained from qRT-PCR and ChIP analyses showed that MTDH considerably inhibited RKIP expression. In addition, the RKIP transcript levels in MTDH-knockdown or MTDH-overexpressing MCF-7 cells were likely correlated to the protein levels, suggesting that MTDH regulates RKIP expression. In conclusion, we suggest that MTDH is a novel factor that controls the RKIP transcription, which is essential for cancer progression.

Phosphatidylethanolamine binding protein 1 enhances sensitivity of gastric cancer cell to 5-fluorouracil via inhibition of cell proliferation, migration and invasion

Purpose: To determine the association between phosphatidylethanolamine binding protein 1, which is an Raf kinase inhibitor protein (RKIP), and 5-fluorouracil (5-FU) via analysis of the association between RKIP and clinical responses in individuals treated using fluorouracil-based chemotherapy.Methods: Human gastric cancer cell lines MGC-803 and SGC-7901 were used in this study. Cell viability was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Apoptosis and migration were determined with flow cytometry and Transwell chamber assays, respectively. The mRNA and protein expressions of apoptosis-related factors were assayed using realtime polymerase chain reaction (RT-PCR) and Western blotting, respectively, while the expression of RKIP was determined by immunohistochemical staining.Results: Chemotherapeutic drug (5-FU) treatment induced low RKIP expression levels in tumorigenic GC cells, thereby sensitizing the cells to apoptosis (8.57 vs 1.25 %, p < 0.01). The highest RKIP level correlated well with initiation of apoptosis (4.20 vs 1.25 %, p < 0.01). Following in vitro downregulation of RKIP, there was increase in the viability and proliferation of RKIP-inhibited cells over time, and these changes were linked to alterations in cell cycle phases and increased optical density in MTT proliferation assay (1.55 vs 1.18, p < 0.01). In vitro Transwell assay measurement revealed an association between RKIP downregulation and enhancement of cell migration potential (652 vs 436, p < 0.01). Ectopic RKIP expression restored the apoptotic sensitivity of resistant cells (14.30 vs 1.36 %, p <0.01). This sensitization was annulled by upregulation of survival routes. Reduction of RKIP by expression of antisense and siRNA conferred resistance on cancer cells sensitive to 5-FU-mediated apoptosis (6.88 vs 2.13 %, p < 0.01).Conclusion: Thus, RKIP is a promising therapeutic strategy for improving the efficacy of clinically relevant chemotherapeutic drugs for GC. Keywords: Gastric cancer, Raf kinase inhibitor protein, Cell proliferation, Invasion, Apoptosis, Chemotherapy, Phosphatidylethanolamine binding protein 1

Diagnostic value of phosphatidylethanolamine binding protein 4 levels in patients receiving nursing interventions for advanced chronic kidney disease

Objective To explore the diagnostic role of phosphatidylethanolamine binding protein 4 (PEBP4) in patients with chronic kidney disease (CKD) receiving nursing interventions. Methods ELISA was used to evaluate serum PEBP4 levels. Receiver-operating characteristic curve analysis was used to assess diagnostic accuracy. Spearman correlation analysis was used to assess the relationships between PEBP4 levels and biochemical indexes. Results Serum PEBP4 was high in CKD patients compared with healthy individuals. PEBP4 levels were positively correlated with pathological stage in CKD patients. PEBP4 had higher sensitivity for diagnosis of CKD than common indexes including blood urea nitrogen, creatinine and C-reactive protein. Among CKD patients treated with calcium channel blockers, serum PEBP4 levels declined notably and were associated with concentrations of K+, Na+, Cl− and Ca2+. Nursing interventions significantly decreased serum PEBP4 levels. A significant association between serum PEBP4 level and ionic concentration was observed in CKD patients receiving nursing interventions. Conclusions This prospective study demonstrated that PEBP4 level might represent an effective diagnostic biomarker in CKD patients. PEBP4 also acted as a valuable care compliance factor for determining the necessity for nursing interventions. Nursing interventions restored ion channel function and subsequently resulted in decreased PEBP4 levels and proteinuria.

PHOSPHATIDYLETHANOLAMINE-BINDING PROTEINS: the conductors of dual reproduction in plants with vegetative storage organs

Geophytes, the plants that form vegetative storage organs, are characterized by a dual reproduction system, in which vegetative and sexual propagation are tightly regulated to ensure fitness in harsh climatic conditions. Recent findings highlight the role of the PEBP (PHOSPHATIDYLETHANOLAMINE-BINDING PROTEIN) gene family in geophytes as major players in the molecular cascades underlying both types of reproduction. In this review, we briefly explain the life cycle and reproduction strategies of different geophytes and what is known about the physiological aspects related to these processes. Subsequently, an in-depth overview is provided of the molecular and genetic pathways driving these processes. In the evolution of plants, the PEBP gene family has expanded, followed by neo- and subfunctionalization. Careful characterization revealed that differential expression and differential protein complex formation provide the members of this gene family with unique functions, enabling them to mediate the crosstalk between the two reproductive events in geophytes in response to environmental and endogenous cues. Taking all these studies into account, we propose to regard the PEBPs as conductors of geophyte reproductive development.

PEBP regulates balance between apoptosis and autophagy, enabling coexistence of arbovirus and insect vector

Apoptosis and autophagy are two most prominent forms of programmed cell deaths (PCD) that have been implicated in antiviral immunity in vertebrate and plant hosts. Arboviruses are able to coexist with its arthropod vectors by coordinating the PCD immunity, but the regulatory mechanism involved is largely unknown. We found that the coat protein (CP) of an insect-borne plant virus TYLCV directly interacted with a phosphatidylethanolamine-binding protein (PEBP) of its insect vector whitefly to negatively influence the MAPK signaling cascade. As a result, the apoptosis was activated in whitefly which increased viral loading. Simultaneously, the PEBP4-CP interaction liberated ATG8, the hallmark of autophagy initiation, and eliminates arbovirus. Furthermore, apoptosis-promoted virus loading was compromised by agonist-induced autophagy, but autophagy-associated suppression on virus loading was unaffected by apoptosis agonist or inhibitor, suggesting that virus loading was predominantly determined by autophagy rather than by apoptosis. Our results demonstrated that maintaining a mild immune response by coordinating apoptosis and autophagy processes presumably could facilitate coexistence of the arbovirus and its insect vector. Taken together, immune homeostasis shaped by two types of PCD may facilitate the arbovirus preservation within the insect vector.Graphical abstractHighlightsInteraction between whitefly PEBP4 and TYLCV CP suppresses phosphorylation of MAPK cascade, activating apoptosisTYLCV CP liberates PEBP4-bound ATG8, resulting in lipidation of ATG8 and initiation of autophagy.PEBP4 balances apoptosis and autophagy in viruliferous whitefly to optimize virus loading without obvious fitness cost.