RESUMEN
The review contains data on the diversity of endogenous ligands of RAGE receptors (receptor for advanced glycation end products) that play an important role in the signal transduction in (patho) physiological conditions. RAGE takes part in various physiological processes like cell growth and survival, apoptosis and regeneration. They serve as regulators of inflammatory reactions due to their ability to induce secretion of cytokines and chemokines. In addition, they facilitate elimination of apoptotic cells and mediate innate immune response. We discuss mechanisms of soluble RAGE production as well as the role of membrane and soluble forms of the receptor in cell signaling. Several endogenous ligands of RA GE are well-known: advanced glycation end products (AGE), amyloid-beta (Aß), nuclear high mobility group box 1 proteins (HMGB1), and calcium-binding proteins S100A4, S100A8/A9, S100A12 u S100B. The review is focused on the mechanisms of the ligands production, their secretion from the cells of various origin, interaction with RAGE, and associated intracellular signal transduction pathways. Special attention is paid to the role of RAGE in pathogenesis of inflammation, particularly, in brain injury and neurodegeneration.
Asunto(s)
Comunicación Celular , Inflamación/metabolismo , Receptor para Productos Finales de Glicación Avanzada/fisiología , Humanos , Ligandos , Transducción de SeñalRESUMEN
The review contains current data on molecular mechanisms which control NAD+ homeostasis in brain cells. It also deals with the role of NAD+-converting enzymes in regulation of functional activity, viability and intercellular communication of neuronal and glial cells. Special attention is paid to involvement of CD38 into regulation of NAD+ levels in brain cells in normal and pathological conditions.
Asunto(s)
ADP-Ribosil Ciclasa 1/farmacología , Encéfalo/enzimología , NAD+ Nucleosidasa/metabolismo , Neuroglía/enzimología , Neuronas/enzimología , Animales , Encéfalo/efectos de los fármacos , Comunicación Celular , Células Cultivadas , Humanos , Neuroglía/citología , Neuroglía/efectos de los fármacos , Neuronas/citología , Neuronas/efectos de los fármacosRESUMEN
The aim of this work was to evaluate contribution of released membrane particles (RMP) to the development of systemic inflammatory response (SIR) after aortocoronary bypass grafting (ACBG). The number of RMP carrying surface adhesion molecules, CD62L, CD62P, CD62E, was shown to increase in the early postoperative period in parallel with the enhancement of lymphocyte plasma membrane blebbing and elevation of cytokine levels in peripheral blood. It is concluded that (1) activation of plasma membrane blebbing in peripheral blood cells underlies the appearance of RMP in circulation; (2) increased number of RMP expressing CD62L, CD62P, CD62E is a marker of intercellular communication associated with the development of SIR and suggests new mechanisms of RMP involvement in the reaction of organism to massive surgical injury.
Asunto(s)
Micropartículas Derivadas de Células/metabolismo , Síndrome de Respuesta Inflamatoria Sistémica/sangre , Puente de Arteria Coronaria/efectos adversos , Citocinas/sangre , Selectina E/sangre , Humanos , Selectina L/sangre , Linfocitos/metabolismo , Linfocitos/ultraestructura , Selectina-P/sangre , Periodo Posoperatorio , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Síndrome de Respuesta Inflamatoria Sistémica/inmunologíaRESUMEN
The pathogenesis of neuronal dysfunction was evaluated from the viewpoint of cellular disturbances in NAD(+) metabolism and changes in activity of NAD(+)-utilizing enzymes (e.g., ADP-ribosyl cyclase/CD38). S-100B concentration and CD38 expression on peripheral blood lymphocytes were altered in patients after surgery for coronary heart disease with extracorporeal circulation. These changes in patients during the early postoperative period correlated with variations in CD38 expression on neuronal cells from postischemic rats with cognitive dysfunction.
Asunto(s)
ADP-Ribosil Ciclasa/fisiología , Puente de Arteria Coronaria , Neuronas/enzimología , ADP-Ribosil Ciclasa/metabolismo , ADP-Ribosil Ciclasa 1/metabolismo , Animales , Encéfalo/citología , Humanos , Inmunoensayo , Isquemia/metabolismo , Isquemia/fisiopatología , Masculino , NAD/metabolismo , Factores de Crecimiento Nervioso/metabolismo , Neuronas/patología , Periodo Posoperatorio , Ratas , Subunidad beta de la Proteína de Unión al Calcio S100 , Proteínas S100/metabolismoRESUMEN
The expression of connexin 43 and CD38 and ADP ribosyl cyclase activity in brain cells were studied in rats with experimental hypoxic and ischemic damage to the CNS. Changes in the expression and activity of the enzyme were detected over the course of ischemic injury indicating a possible contribution of NAD(+)-converting activity and NAD(+)-transporting processes to the pathogenesis of acute cerebral ischemic injury.
Asunto(s)
ADP-Ribosil Ciclasa 1/metabolismo , ADP-Ribosil Ciclasa/metabolismo , Isquemia Encefálica/fisiopatología , Sistema Nervioso Central/metabolismo , Conexina 43/metabolismo , Regulación de la Expresión Génica , Hipoxia/fisiopatología , Animales , Animales Recién Nacidos , Encéfalo/metabolismo , Encéfalo/patología , Sistema Nervioso Central/patología , Regulación Enzimológica de la Expresión Génica , Inmunohistoquímica , RatasRESUMEN
We studied the mechanism of interaction of peripheral blood neutrophils with endothelial cells (expression of cell adhesion molecules and production of NO) and the role of neutrophil apoptosis in the development of endothelial dysfunction. The effects of mitochondrial dysfunction of neutrophils on the development of apoptosis of these cells after their interaction with endothelial cells were analyzed.