ABSTRACT
The Gαq/phospholipase C-ß (PLCß) signaling system mediates calcium responses to a variety of hormones and neurotransmitters. Recent studies suggest that PLCß1 expression plays a role in the differentiation of two types of cultured neuronal cells (PC12 and SK-N-SH) through a mechanism independent of Gαq. Here, we show that, similar to that observed in PC12 and SK-N-SH cells, PLCß1 expression increases when human NT2 cells are induced to differentiate either through cytosine-ß-D-arabinofuranoside or retinoic acid. Preventing this increase, abolishes differentiation, and down-regulating PLCß1 in rat primary astrocytes causes cells to adapt an undifferentiated morphology. Surprisingly, transfecting PLCß1 into undifferentiated PC12 or NT2 cells induces differentiation without the need for differentiating agents. Studies to uncover the underlying mechanism focused on the transcription factor early growth response 1 (Egr-1) which mediates PLCß1 expression early in differentiation. Over-expressing PLCß1 in HEK293 cells enhances Egr-1 expression and induces morphological changes. We show that increased levels of cytosolic PLCß1 in undifferentiated PC12 cells disrupts the association between Egr-1 and its cytosolic binding partner (Tar RNA binding protein), promoting relocalization of Egr-1 to the nucleus, which promotes transcription of proteins needed for differentiation. These studies show a novel mechanism through which differentiation can be modulated.
ABSTRACT
Fundamento y objetivo: Estimar el exceso de riesgo de mortalidad por cáncer de pulmón asociado a la exposición al humo ambiental del tabaco (HAT) en trabajadores de hostelería a partir de mediciones objetivas de las concentraciones de HAT en locales de hostelería de Barcelona. Método: Se midió la concentración de nicotina en fase vapor en establecimientos de hostelería. Las concentraciones de nicotina se utilizaron para estimar el exceso de riesgo de mortalidad por cáncer de pulmón durante un período laboral de 40 años mediante la fórmula desarrollada por Repace y Lowrey. Resultados: El exceso de riesgo de mortalidad por cáncer de pulmón asociado a la exposición al HAT supera las 145 muertes por cada 100.000 trabajadores en todos los lugares estudiados, a excepción de las cafeterías de hospital, donde es de 22 por 100.000. En el caso de las discotecas, alcanza las 1.733 muertes por cada 100.000 trabajadores. Conclusión: Los trabajadores de hostelería están expuestos a unas concentraciones de HAT que suponen un exceso de riesgo de mortalidad por cáncer de pulmón muy elevado. Se confirma la necesidad de medidas de control del HAT que protejan a los trabajadores de la hostelería
Background and objective: To estimate the excess lung cancer mortality risk associated with environmental tobacco (ETS) smoke exposure among hospitality workers. The estimation was done using objective measures in several hospitality settings in Barcelona. Method: Vapour phase nicotine was measured in several hospitality settings. These measurements were used to estimate the excess lung cancer mortality risk associated with ETS exposure for a 40 year working life, using the formula developed by Repace and Lowrey. Results: Excess lung cancer mortality risk associated with ETS exposure was higher than 145 deaths per 100 000 workers in all places studied, except for cafeterias in hospitals, where excess lung cancer mortality risk was 22 per 100 000. In discoteques, for comparison, excess lung cancer mortality risk is 1,733 deaths per 100 000 workers. Conclusion: Hospitality workers are exposed to ETS levels related to a very high excess lung cancer mortality risk. These data confirm that ETS control measures are needed to protect hospital workers