RESUMEN
Insulin-degrading enzyme (IDE) is a highly conserved zinc metallopeptidase that is ubiquitously distributed in human tissues, and particularly abundant in the brain, liver, and muscles. IDE activity has been historically associated with insulin and ß-amyloid catabolism. However, over the last decade, several experimental findings have established that IDE is also involved in a wide variety of physiopathological processes, including ubiquitin clearance and Varicella Zoster Virus infection. In this study, we demonstrate that normal and malignant cells exposed to different stresses markedly up-regulate IDE in a heat shock protein (HSP)-like fashion. Additionally, we focused our attention on tumor cells and report that (i) IDE is overexpressed in vivo in tumors of the central nervous system (CNS); (ii) IDE-silencing inhibits neuroblastoma (SHSY5Y) cell proliferation and triggers cell death; (iii) IDE inhibition is accompanied by a decrease of the poly-ubiquitinated protein content and co-immunoprecipitates with proteasome and ubiquitin in SHSY5Y cells. In this work, we propose a novel role for IDE as a heat shock protein with implications in cell growth regulation and cancer progression, thus opening up an intriguing hypothesis of IDE as an anticancer target.
Asunto(s)
Insulisina/fisiología , Neoplasias Encefálicas/metabolismo , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Secuencia Conservada , Regulación hacia Abajo , Proteínas de Choque Térmico/metabolismo , Humanos , Inmunohistoquímica/métodos , Insulina/metabolismo , Insulisina/metabolismo , Células Jurkat , Metaloproteasas/química , Microscopía Fluorescente/métodos , Neuroblastoma/metabolismo , ARN Interferente Pequeño/metabolismo , Factores de TiempoRESUMEN
The new allele HLA-C*07:852 differs from HLA-C* 07:04:01:01 by one nucleotide substitution in codon 314 in exon 5.
Asunto(s)
Genes MHC Clase I , Antígenos HLA-C , Humanos , Antígenos HLA-C/genética , Alelos , Codón , Exones/genética , Análisis de Secuencia de ADN , Prueba de HistocompatibilidadRESUMEN
HLA-DRB3*02:202 differs from DRB3*02:112 by one nucleotide substitution in codon 51 in exon 2.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Cadenas HLA-DRB3 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Prueba de Histocompatibilidad/métodos , Análisis de Secuencia de ADN/métodos , Cadenas HLA-DRB3/genética , Codón , Alineación de SecuenciaRESUMEN
HLA-DQB1*06:02:61 differs from HLA-DQB1*06:02:01:01 by one nucleotide substitution in exon 4-5512 G>A.
Asunto(s)
Alelos , Exones , Cadenas beta de HLA-DQ , Secuenciación de Nucleótidos de Alto Rendimiento , Prueba de Histocompatibilidad , Humanos , Cadenas beta de HLA-DQ/genética , Prueba de Histocompatibilidad/métodos , Secuencia de Bases , Análisis de Secuencia de ADN/métodos , Polimorfismo de Nucleótido SimpleRESUMEN
HLA-A*02:01:189 differs from HLA-A*02:01:01:01 by one nucleotide substitution in Exon 3, codon 101 TGC > TGT.
Asunto(s)
Alelos , Secuencia de Bases , Exones , Antígeno HLA-A2 , Prueba de Histocompatibilidad , Análisis de Secuencia de ADN , Humanos , Antígeno HLA-A2/genética , Antígeno HLA-A2/inmunología , Análisis de Secuencia de ADN/métodos , Codón , Alineación de Secuencia , Polimorfismo de Nucleótido SimpleRESUMEN
In current clinical practice, transplant clinicians create collaborative working relationships with histocompatibility laboratory scientists to identify the risk of long-term graft failure, which may assist in establishing strategies for treatment and surveillance. Transplant immunology research also focuses on optimizing human leukocyte antibody tissue typing and defines the most effective test for detecting the presence of donor-specific antibodies. Although several studies have been conducted, data on pediatric heart transplant recipients are limited. Epitope load information may be utilized to identify donors with permissible human leukocyte antibody mismatches to increase transplant success. Although current guidelines do not consider human leukocyte antibody epitope-based matching tools, these guidelines could be useful for identifying recipients at a high risk of donor-specific antibody production, which would be appropriate for routine donor-specific antibody screening to initiate early interventions to prevent antibody-mediated rejection. Human leukocyte antibody matching at the epitope level offers an effective approach for identifying acceptable mismatches in sensitized patients and provides information about epitope loads. In the future, eplet matching may be used to define the best immunosuppressive therapy protocol for cardiothoracic organ transplantation. This report provides an overview of the role of human leukocyte antibodies in heart and lung transplantation.
Asunto(s)
Anticuerpos , Donantes de Tejidos , Humanos , Niño , Alelos , Selección de Donante , EpítoposRESUMEN
The novel HLA-DPA1*01:149 allele differs from HLA-DPA1*01:03:01:05 by one nucleotide substitution in exon 2.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
The novel HLA-DPA1*02:110:02 allele differs from HLA-DPA1*02:01:01:06 by one nucleotide substitution in exon 4.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Alelos , Prueba de Histocompatibilidad , Cadenas alfa de HLA-DP/genéticaRESUMEN
HLA-DQA1*01:89 differs from HLA-DQA1*01:01:01:01 by one nucleotide substitution in codon -5 in exon 1.
Asunto(s)
Alelos , Humanos , Cadenas alfa de HLA-DQ/genética , Análisis de Secuencia de ADN , Exones/genéticaRESUMEN
HLA-DRB1*11:04:21 differs from HLA-DRB1*11:04:01 by one nucleotide substitution in codon 69 in exon 2.
Asunto(s)
Cadenas HLA-DRB1 , Alelos , Secuencia de Bases , Exones/genética , Cadenas HLA-DRB1/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
HLA-DQA1*01:76 differs from HLA-DQA1*01:03:01:06 by one nucleotide substitution in codon -11 in exon 1.
Asunto(s)
Alelos , Exones/genética , Cadenas alfa de HLA-DQ/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
The novel HLA-DPA1*02:53 allele differs from HLA-DPA1*02:01:01:02 by one nucleotide substitution in exon 3.
Asunto(s)
Cadenas alfa de HLA-DP , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Exones/genética , Cadenas alfa de HLA-DP/genética , HumanosRESUMEN
The novel allele HLA-B*07:422 differs from HLA-B*07:02:01:01 by one nucleotide substitution in exon 4.
Asunto(s)
Antígeno HLA-B7 , Secuenciación de Nucleótidos de Alto Rendimiento , Alelos , Exones/genética , HumanosRESUMEN
HLA-A*30:181 differs from HLA-A*30:01:01 by one nucleotide substitution in Exon 4832 G to A.
Asunto(s)
Secuenciación de Nucleótidos de Alto Rendimiento , Mutación Missense , Alelos , Exones/genética , Antígenos HLA-A/genética , HumanosRESUMEN
HLA-DQA1*03:20 differs from HLA-DQA1*03:03:01:01 by one nucleotide substitution in codon 33 in exon 2.
Asunto(s)
Alelos , Exones/genética , Cadenas alfa de HLA-DQ/genética , Humanos , Análisis de Secuencia de ADNRESUMEN
HLA-B*44:02:68 differs from B*44:02:01:01 by one synonmous nucleotide substitution in codon-10 GGG- > GGA.