Last update 19 Sep 2024

BPIFA1

Last update 19 Sep 2024

Basic Info

Synonyms

bA49G10.5, BPI fold containing family A member 1, BPI fold-containing family A member 1

+ [13]

Introduction

Lipid-binding protein which shows high specificity for the surfactant phospholipid dipalmitoylphosphatidylcholine (DPPC) (PubMed:25223608). Plays a role in the innate immune responses of the upper airways (PubMed:23499554, PubMed:23132494). Reduces the surface tension in secretions from airway epithelia and inhibits the formation of biofilm by pathogenic Gram-negative bacteria, such as P.aeruginosa and K.pneumoniae (PubMed:23499554, PubMed:23132494, PubMed:27145151). Negatively regulates proteolytic cleavage of SCNN1G, an event that is required for activation of the epithelial sodium channel (ENaC), and thereby contributes to airway surface liquid homeostasis and proper clearance of mucus (PubMed:24124190, PubMed:24043776). Plays a role in the airway inflammatory response after exposure to irritants (PubMed:11425234). May attract macrophages and neutrophils (PubMed:23132494).

Drugs associated with BPIFA1

ELD-607

Target

BPIFA1 x ORAI1

Mechanism

BPIFA1 stimulators [+1]

Active Org.

Eldec Pharmaceuticals, Inc.

Originator Org.

Eldec Pharmaceuticals, Inc.

Active Indication

Enterobacter Infection [+5]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with BPIFA1

100 Translational Medicine associated with BPIFA1

0 Patents (Medical) associated with BPIFA1

275

Literatures (Medical) associated with BPIFA1

01 Nov 2024·Cell Calcium

ELD607 specifically traffics Orai1 to the lysosome leading to inhibition of store operated calcium entry

Article

Author: Wrennall, Joe A ; Tarran, Robert ; Flori Sassano, M ; Goriounova, Alexandra S

Orai1 is a plasma membrane Ca²⁺ channel involved in store operated calcium entry (SOCE). SOCE can regulate cell growth, exocytosis, gene expression and inflammation. We previously found that short palate lung and nasal epithelial clone 1's (SPLUNC1) sixth α-helix (α6) bound Orai1 to inhibit SOCE. SPLUNC1 was not proteolytically stable, so we developed ELD607, an 11 amino acid peptide based on SPLUNC1's α6 region which was more stable and more potent than SPLUNC1/α6. Here, we studied ELD607's mechanism of action. We overexpressed either Orai1-HA or Orai1-YFP in HEK293T cells to probe ELD607-Orai1 interactions by confocal microscopy. We also measured changes in Fluo-4 fluorescence in a multiplate reader as a marker of cytoplasmic Ca²⁺ levels. ELD607 internalized Orai1 independently of STIM1. Both 15 min and 3 h exposure to ELD607 similarly depleted Orai1 in the plasma membrane. However, 3 h exposure to ELD607 yielded greater inhibition of SOCE. ELD607 continued to colocalize with Orai1 after internalization and this process was dependent on the presence of the ubiquitin ligase NEDD4.2. Similarly, ELD607 increased the colocalization between Orai1 and ubiquitin. ELD607 also increased the colocalization between Orai1 and Rab5 and 7, but not Rab11, suggesting that Orai1 trafficked through early and late but not recycling endosomes. Finally, ELD607 caused Orai1, but not Orai2, Orai3, or STIM1 to traffic to lysosomes. We conclude that ELD607 rapidly binds to Orai1 and works in an identical fashion as full length SPLUNC1 by internalizing Orai1 and sending it to lysosomes, leading to a decrease in SOCE.

13 May 2024·Biomacromolecules

Correction to “Lung SPLUNC1 Peptide Derivatives in the Lipid Membrane Headgroup Kill Gram-Negative Planktonic and Biofilm Bacteria”

Author: Vijai, Aishwarya ; Gong, Yuqi ; Di, Yuan-Pu ; Qin, Weiheng ; Kang, Ann ; Mitra, Saheli ; Lin, Qiao ; Chen, Jespar ; Tristram-Nagle, Stephanie ; Jakkampudi, Tanvi ; Wang, Runxuan ; Ryan, Emma ; Heinrich, Frank ; Song, Junming

SPLUNC1 (short palate lung and nasal epithelial clone 1) is a multifunctional host defense protein found in human respiratory tract with antimicrobial properties.In this work, we compare the biol. activities of four SPLUNC1 antimicrobial peptide (AMP) derivatives using paired clin. isolates of the Gram-neg. (G(-)) bacteria Klebsiella pneumoniae, obtained from 11 patients with/without colistin resistance.Secondary structural studies were carried out to study interactions between the AMPs and lipid model membranes (LMMs) utilizing CD (CD).Two peptides were further characterized using X-ray diffuse scattering (XDS) and neutron reflectivity (NR).A4-153 displayed superior antibacterial activity in both G(-) planktonic cultures and biofilms.NR and XDS revealed that A4-153 (highest activity) is located primarily in membrane headgroups, while A4-198 (lowest activity) is located in hydrophobic interior.CD revealed that A4-153 is helical, while A4-198 has little helical character, demonstrating that helicity and efficacy are correlated in these SPLUNC1 AMPs.

01 May 2024·Schizophrenia Research

The expression of immune related genes and potential regulatory mechanisms in schizophrenia

Article

Author: Ou, Mengmeng ; Yuan, Jianming ; Yu, Shui ; Lu, Rongrong ; Zhu, Haohao ; Qu, Yucai ; Du, Zhiqiang ; Jiang, Ying

OBJECTIVEThis study aimed to investigate the role of immune dysfunction in the pathogenesis of schizophrenia through single-cell transcriptome and bulk RNA data analyses.METHODSThe single-cell RNA sequencing (scRNA-seq) was selected to assess the cellular composition and gene expression profiles of the brain tissue. Further, bulk RNA sequencing data was utilized to corroborate findings from the single-cell analyses and provide additional insights into the molecular changes associated with the disease. Gene-drug interaction data was also included to identify potential therapeutic drugs targeting these dysregulated immune-related genes in schizophrenia.RESULTSWe discovered significant differences in cellular composition within schizophrenia tissue, including increased infiltration of fibroblasts, horizontal basal cells, monocytes, mesenchymal cells, and smooth muscle cells. The investigation of immune-related genes revealed significantly different expression of genes such as S100A2, CCL14, IGHA1, BPIFA1, GDF15, IL32, BPIFB2, HLA-DRA, S100A8, PTX3, TPM2, TNFRSF12A, GREM1 and others. These genes possibly contribute to the progression of schizophrenia through various pathways such as humoral immune response, IL-17 signaling pathway, adaptive immune response, antigen processing and presentation, and gut IgA production. Our findings also suggest possible transcriptional regulation in schizophrenia's immune dysfunction by transcription factors in monocytes, neutrophils, endothelial cells, and epithelial cells. Lastly, potential therapeutic drugs were identified through gene-drug interaction data, such as those targeting HLA-A and HLAB.CONCLUSIONThe cellular heterogeneity and immune-related gene dysregulation play important roles in schizophrenia, which provides a foundation for understanding the pathogenesis and developing new treatment methods.

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BPIFA1

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