scholarly journals Coexpression of novel furin-resistant LPL variants with lipase maturation factor 1 enhances LPL secretion and activity

2018 ◽  
Vol 59 (12) ◽  
pp. 2456-2465 ◽  
Author(s):  
Ming Jing Wu ◽  
Anna Wolska ◽  
Benjamin S. Roberts ◽  
Ellis M. Pearson ◽  
Aspen R. Gutgsell ◽  
...  
Keyword(s):  
Maturation Factor ◽  
Lipase Maturation Factor 1

scholarly journals Sperm cryopreservation impacts the early development of equine embryos by downregulating specific transcription factors

2021 ◽  
Author(s):  
Jose Manuel Ortiz-Rodriguez ◽  
Francisco Eduardo Martin-Cano ◽  
Gemma L Gaitskell-Phillips ◽  
Alberto Alvarez Barrientos ◽  
Heriberto Rodriguez-Martínez ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Enrichment Analysis ◽  
Sperm Cryopreservation ◽  
Pseudouridine Synthase ◽  
Maturation Factor ◽  
Human Orthologs ◽  
Specific Factors ◽  
Lipase Maturation Factor 1 ◽  
Next Generation Sequencing Ngs ◽  
Generation Sequencing

Equine embryos were obtained by insemination with either fresh or frozen-thawed spermatozoa at 8, 10 and 12 h post spontaneous ovulation, maintaining the pairs mare-stallion for the type of semen used. Next generation sequencing (NGS) was performed in all embryos and bioinformatic and enrichment analysis performed on the 21,058 identified transcripts. A total of 165 transcripts were downregulated in embryos obtained with cryopreserved spermatozoa respect embryos resulting from an insemination with fresh spermatozoa (p=0.021, q=0.1). The enrichment analysis using human orthologs using g:profiler on the downregulated transcripts marked an enrichment in transcription factors (TFs) in mRNAs downregulated in embryos obtained after insemination with cryopreserved spermatozoa. The 12 mRNAs (discriminant variables) most significantly downregulated in these embryos included among others, the chromatin-remodeling ATPase INO80, Lipase maturation factor 1 LMF1, the mitochondrial mRNA pseudouridine synthase RPUSD3, LIM and cysteine-rich domains protein 1, LMCD1. Sperm cryopreservation also caused a significant impact on the embryos at 8 to 10 days of development, but especially in the transition from 10 to 12 days. Overall, our findings provide strong evidence that insemination with cryopreserved spermatozoa poses a major impact in embryo development that may compromise its growth and viability, probably due to modifications in sperm proteins induced by cryopreservation. Identification of specific factors in the spermatozoa causing these changes may improve cryopreservation.

scholarly journals Structure of lipoprotein lipase in complex with GPIHBP1

2019 ◽  
Vol 116 (21) ◽  
pp. 10360-10365 ◽  
Author(s):  
Rishi Arora ◽  
Amitabh V. Nimonkar ◽  
Daniel Baird ◽  
Chunhua Wang ◽  
Chun-Hao Chiu ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Lipoprotein Lipase ◽  
Structural Information ◽  
Density Lipoprotein ◽  
Lipid Binding ◽  
Structural Basis ◽  
Maturation Factor ◽  
Lipase Maturation Factor 1 ◽  
Hydrolysis Of

Lipoprotein lipase (LPL) plays a central role in triglyceride (TG) metabolism. By catalyzing the hydrolysis of TGs present in TG-rich lipoproteins (TRLs), LPL facilitates TG utilization and regulates circulating TG and TRL concentrations. Until very recently, structural information for LPL was limited to homology models, presumably due to the propensity of LPL to unfold and aggregate. By coexpressing LPL with a soluble variant of its accessory protein glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) and with its chaperone protein lipase maturation factor 1 (LMF1), we obtained a stable and homogenous LPL/GPIHBP1 complex that was suitable for structure determination. We report here X-ray crystal structures of human LPL in complex with human GPIHBP1 at 2.5–3.0 Å resolution, including a structure with a novel inhibitor bound to LPL. Binding of the inhibitor resulted in ordering of the LPL lid and lipid-binding regions and thus enabled determination of the first crystal structure of LPL that includes these important regions of the protein. It was assumed for many years that LPL was only active as a homodimer. The structures and additional biochemical data reported here are consistent with a new report that LPL, in complex with GPIHBP1, can be active as a monomeric 1:1 complex. The crystal structures illuminate the structural basis for LPL-mediated TRL lipolysis as well as LPL stabilization and transport by GPIHBP1.

scholarly journals Withdrawal: Lipase maturation factor 1 is required for endothelial lipase activity

2019 ◽  
Vol 60 (9) ◽  
pp. 1641-1641
Author(s):  
Osnat Ben-Zeev ◽  
Maryam Hosseini ◽  
Ching-Mei Lai ◽  
Nicole Ehrhardt ◽  
Howard Wong ◽  
...  
Keyword(s):  
Lipase Activity ◽  
Endothelial Lipase ◽  
Maturation Factor ◽  
Lipase Maturation Factor 1

scholarly journals Lipase maturation factor 1: structure and role in lipase folding and assembly

2010 ◽  
Vol 21 (3) ◽  
pp. 198-203 ◽  
Author(s):  
Mark H Doolittle ◽  
Nicole Ehrhardt ◽  
Miklós Péterfy
Keyword(s):  
Maturation Factor ◽  
Lipase Maturation Factor 1

scholarly journals Novel LMF1 Nonsense Mutation in a Patient with Severe Hypertriglyceridemia

2009 ◽  
Vol 94 (11) ◽  
pp. 4584-4590 ◽  
Author(s):  
Angelo B. Cefalù ◽  
Davide Noto ◽  
Maria Luisa Arpi ◽  
Fen Yin ◽  
Rossella Spina ◽  
...  
Keyword(s):  
Nonsense Mutation ◽  
Stop Codon ◽  
Hepatic Lipase ◽  
Premature Stop Codon ◽  
Pathogenic Mutation ◽  
Response To Treatment ◽  
Severe Hypertriglyceridemia ◽  
Maturation Factor ◽  
Exon 9 ◽  
Lipase Maturation Factor 1

Context: Lipase maturation factor 1 (LMF1) gene is a novel candidate gene in severe hypertriglyceridemia. Lmf1 is involved in the maturation of lipoprotein lipase (LPL) and hepatic lipase in endoplasmic reticulum. To date only one patient with severe hypertriglyceridemia and related disorders was found to be homozygous for a nonsense mutation in LMF1 gene (Y439X). Objective: The objective of the study was to investigate LMF1 gene in hypertriglyceridemic patients in whom mutations in LPL, APOC2, and APOA5 genes had been excluded. Results: The resequencing of LMF1 gene led to the discovery of a novel homozygous nonsense mutation in one patient with severe hypertriglyceridemia and recurrent episodes of pancreatitis. The mutation causes a G>A substitution in exon 9 (c.1395G>A), leading to a premature stop codon (W464X). LPL activity and mass were reduced by 76 and 50%, respectively, compared with normolipidemic controls. The proband over the years has shown a good response to treatment. The proband’s son, heterozygous for the W464X, shows normal plasma triglyceride levels. Conclusions: We identified the second novel pathogenic mutation in LMF1 gene in a patient with severe hypertriglyceridemia. LPL deficiency in our patient was milder than in the carrier of the Y439X previously described. Identification and functional analysis of a novel nonsense mutation of the LMF1 gene in a patient with severe hypertriglyceridemia.

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