• International Journal of Industrial Entomology and Biomaterials
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• v.19 no.2
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• pp.229-235
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• 2009

We have cloned and characterized a lipocalin from the bumblebee Bombus ignitus (Bi-lipocalin). The Bi-lipocalin gene spans 2284 bp and consists of four exons coding for 270 amino acid residues. Sequence analysis revealed that Bi-lipocalin possesses three structurally conserved regions (SCTs) that characterize lipocalins. Recombinant Bi-lipocalin, expressed as a 37 kDa protein in baculovirus-infected insect cells, was N-glycosylated, indicating that the carbohydrate moieties are necessary for secretion. Tissue distribution analysis revealed ubiquitous expression of Bi-lipocalin in all tissues examined. Bi-lipocalin transcripts were upregulated by stress, such as wounding, $H_2O_2$ exposure, and external temperature shock. These results indicate that Bi-lipocalin is a stress-inducible protein that acts on wounding, $H_2O_2$ overexposure and temperature stimulation.

• BMB Reports
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• v.56 no.12
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• pp.669-674
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• 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to various clinical symptoms including anemia. Lipocalin-2 has various biological functions, including defense against bacterial infections through iron sequestration, and it serves as a biomarker for kidney injury. In a human protein array, we observed increased lipocalin-2 expression due to parental SARS-CoV-2 infection in the Calu-3 human lung cancer cell line. The secretion of lipocalin-2 was also elevated in response to parental SARS-CoV-2 infection, and the SARS-CoV-2 Alpha, Beta, and Delta variants similarly induced this phenomenon. In a Calu-3 implanted mouse xenograft model, parental SARSCoV-2 and Delta variant induced lipocalin-2 expression and secretion. Additionally, the iron concentration increased in the Calu-3 tumor tissues and decreased in the serum due to infection. In conclusion, SARS-CoV-2 infection induces the production and secretion of lipocalin-2, potentially resulting in a decrease in iron concentration in serum. Because the concentration of iron ions in the blood is associated with anemia, this phenomenon could contribute to developing anemia in COVID-19 patients.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.2
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• pp.407-410
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• 2015

Background: Acute kidney injury is an important issue in chemotherapy receiving patients an neutrophil gelatinase-associated lipocalin has been proposed as a novel marker. We here aimed to assess the role of urinary levels for assessment after platin exposure. Materials and Methods: Patients who had treated with cisplatin or carboplatin or oxaliplatin containg regimens were included in this study. Baseline and postchemotherapy serum urea, creatinine, urine neutrophil gelatinase-associated lipocalin and urine creatinine levels were determined. To avoid the effects of hydration during chemotherapy infusion the urinary neutrophil gelatinase-associated lipocalin/urine creatinine ratio was used to determine acute kidney injury. Results: Of a total of 42 patients receiving platin compounds,14 (33.3%) received cisplatin containing regimens, 14 (33.3%) received carboplatin and 14 (33.3%) oxaliplatin. The median age was 60 (37-76) years. Nineteen of the patients (45.2%) had lung cancer, 12 (28.6%) colorectal cancer and 11 (26.2%) others. The median pre and post chemotherapy urine neutrophil gelatinase-associated lipocalin/urine creatinin ratio was 15.6 ng/mg and 35.8 ng/mg (p=0.041) in the cisplatin group, 32.5 ng/mg and 86.3 ng/mg (p=0.004) in the carboplatin group and 40.9 ng/mg and 62.3 ng/mg (p=0.243) in the oxaliplatin group. Conclusions: Nephrotoxicity is a serious side effect of chemotherapeutic agentslike cisplatin and carbopaltin, but only to a lower extent oxaliplatin. All platin compounds must be used carefully and urine neutrophil gelatinase-associated lipocalin measurement seems to be promising in detecting acute kidney injury earlier than with creatinine.

• Childhood Kidney Diseases
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• v.19 no.2
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• pp.79-88
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• 2015

Neutrophil gelatinase-associated lipocalin (NGAL) has emerged as one of the most promising biomarkers of renal epithelial injury. Numerous studies have presented the diagnostic and prognostic utility of urinary and plasma NGAL in patients with acute kidney injury, chronic kidney disease, renal injury after kidney transplantation, and other renal diseases. NGAL is a member of the lipocalin family that is abundantly expressed in neutrophils and monocytes/macrophages and is a mediator of the innate immune response. The biological significance of NGAL to hamper bacterial growth by sequestering iron-binding siderophores has been studied in a knock-out mouse model. Besides neutrophils, NGAL is detectable in most tissues normally encountered by microorganisms, and its expression is upregulated in epithelial cells during inflammation. A growing number of studies have supported the clinical utility of NAGL for detecting invasive bacterial infections. Several investigators including our group have reported that measuring NGAL can be used to help predict and manage urinary tract infections and acute pyelonephritis. This article summarizes the biology and pathophysiology of NGAL and reviews studies on the implications of NGAL in various renal diseases from acute kidney injury to acute pyelonephritis.

• IMMUNE NETWORK
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• v.13 no.6
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• pp.289-294
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• 2013

Lipocalin-2 (LCN2) is an acute-phase protein induced by injury, infection, or other inflammatory stimuli. LCN2 binds small hydrophobic ligands and interacts with cell surface receptor to regulate diverse cellular processes. The role of LCN2 as a chemokine inducer in the central nervous system (CNS) has been previously reported. Based on the previous participation of LCN2 in neuroinflammation, we investigated the role of LCN2 in formalin-induced nociception and pathological pain. Formalin-induced nociceptive behaviors (licking/biting) and spinal microglial activation were significantly reduced in the second or late phase of the formalin test in Lcn2 knockout mice. Likewise, antibody-mediated neutralization of spinal LCN2 attenuated the mechanical hypersensitivity induced by peripheral nerve injury in mice. Taken together, our results suggest that LCN2 can be therapeutically targeted, presumably for both prevention and reversal of acute inflammatory pain as well as pathological pain.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.3
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• pp.301-309
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• 2018

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

• Bulletin of the Korean Chemical Society
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• v.29 no.5
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• pp.959-962
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• 2008

We have performed FlexX docking experiments to predict the best docking poses of 5-androst-16-en-3-ol or 5-androst-16-en-3-one to Boar salivary lipocalin (SAL). Since no steroids were found inside of the binding pocket of the X-ray structure of 1GM6, we tried to find docking structures after opening the pocket using the random tweak option implemented in SYBYL. This operation allowed the ligand to enter the pocket. The best poses generated from FlexX were different from the structures reported earlier, which calculated docking poses by manual docking followed by minimization. Analysis of docking poses allowed us to identify pharmacophores. From this information, virtual screening experiments using UNITY were performed. Among six candidates, 3-(3,7-dimethyloct-6-enylamino)propane-1,2-diol (Leadquest code name: 5755) was chosen for further development. Future work will involve synthesis of some derivatives of 5755 and biological experiments if any derivatives can control the biostimulation and improve reproductive efficiency in pigs.

• Childhood Kidney Diseases
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• v.23 no.2
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• pp.105-110
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• 2019

Purpose: We sought to determine associations of urinary neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP), known markers of renal injury, with hematuria in children and adolescents. Methods: A total of 112 urine samples from 72 patients aged 2 to 18 years with hematuria were enrolled in this study. Urinary concentrations of NGAL and L-FABP were measured by ELISA and compared between subjects with and without proteinuria and between subjects with and without glomerulonephritis diagnosed by renal biopsy. Results: Urinary concentrations of NGAL and L-FABP/creatinine (Cr) in subjects with proteinuria were not significantly different from those in subjects without proteinuria. They were not significant different between subjects with and without glomerulonephritis either. However, both concentrations of urinary NGAL and L-FABP/Cr were positively associated with urinary protein to creatinine ratio. Their levels had a tendency to be increased when proteinuria developed at later visits in subjects with hematuria only at initial visits. Conclusion: Monitoring urinary NGAL and L-FABP levels in addition to conventional risk factors such as proteinuria and serum creatinine might improve the prediction of renal injury in pediatric patients with hematuria.

• Childhood Kidney Diseases
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• v.25 no.2
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• pp.84-91
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• 2021

Purpose: We aimed to study the association of plasma neutrophil gelatinase-associated lipocalin (pNGAL) and leukocyte differential count in children with febrile urinary tract infection (UTI). Methods: Medical records of 154 children aged 1 month to 13 years with febrile UTI who were hospitalized were retrospectively reviewed. Associations between pNGAL levels and blood leukocyte differential count at admission and after 48 hours of treatment were investigated in children with or without acute pyelonephritis (APN). Results: The APN group (n=82) showed higher pNGAL levels, neutrophil count, monocyte count, and neutrophil-to-lymphocyte ratio (NLR), compared to the non-APN group (n=72) (all P<0.05). After adjustment for age and sex, pNGAL showed positive correlations with neutrophil count and NLR in both groups (all P<0.05). Additionally, it was correlated with the monocyte-to-lymphocyte ratio (MLR) only in the APN group (P<0.05). Before and after treatment, pNGAL was positively correlated with neutrophil count, NLR, and MLR in patients with APN while it was related with neutrophil count and NLR in those without APN (all P<0.05). Areas under the receiver operating curve of pNGAL, neutrophil count, NLR, and MLR for predicting APN were 0.804, 0.760, 0.730, and 0.636, respectively (all P<0.05). Only pNGAL was independently associated with the presence of APN in a multivariable logistic regression analysis (P<0.05). Conclusion: In children with febrile UTIs, pNGAL might be associated with leukocyte differential count and the presence of APN.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.1111-1114
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• 2013

Background: For early detection of renal damage during the usage of cisplatin based chemotherapy, changes in renal function should be monitored carefully. In recent years, neutrophil gelatinase-associated lipocalin, a small polypeptide molecule, has shown promise as a marker of acute renal failure. The aim of this present study was to assess possible risk prediction of cisplatin-induced nephrotoxicity using serum NGAL. Materials and Methods: A total of 34 consecutive patients with documented serum creatinine at least 24 hours before every cycle of cisplatin-based chemotherapy were included in the study. Demographic and medical data including age, performance status, tumor characteristics and comorbid diseases were collected from medical charts. Renal function was evaluated at least 48 hours before the treatment and at the end of the treatment based on the Modification of Diet in Renal Disease (MDRD) formula. Before and after cisplatin infusion serum NGAL levels were measured for the first and 3rd cycles of chemotherapy. Results: The median age of the study population was 54 (32-70) years. Fifteen patients (41.1%) were treated on an adjuvant basis, whereas 19 patients (58.9%) were treated for metastatic disease. There was no correlation of serum NGAL levels with serum creatinine (r=0.20, p=0.26) and MDRD (r=-0.12, p=0.50) and creatinine clearance-Cockcroft-Gault (r=-0.22, p=0.22) after cisplatin infusion at the end of the 3rd cycle of chemotherapy. Conclusions: In our study, serum NGAL levels were not correlated with the cisplatin induced nephrotoxicity. Further prospective studies are needed to conclude that serum NGAL level is not a good surrogate marker to predict early cisplatin induced nephrotoxicity.