RESUMEN
NAD metabolism regulates diverse biological processes, including ageing, circadian rhythm and axon survival. Axons depend on the activity of the central enzyme in NAD biosynthesis, nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2), for their maintenance and degenerate rapidly when this activity is lost. However, whether axon survival is regulated by the supply of NAD or by another action of this enzyme remains unclear. Here we show that the nucleotide precursor of NAD, nicotinamide mononucleotide (NMN), accumulates after nerve injury and promotes axon degeneration. Inhibitors of NMN-synthesising enzyme NAMPT confer robust morphological and functional protection of injured axons and synapses despite lowering NAD. Exogenous NMN abolishes this protection, suggesting that NMN accumulation within axons after NMNAT2 degradation could promote degeneration. Ectopic expression of NMN deamidase, a bacterial NMN-scavenging enzyme, prolongs survival of injured axons, providing genetic evidence to support such a mechanism. NMN rises prior to degeneration and both the NAMPT inhibitor FK866 and the axon protective protein Wld(S) prevent this rise. These data indicate that the mechanism by which NMNAT and the related Wld(S) protein promote axon survival is by limiting NMN accumulation. They indicate a novel physiological function for NMN in mammals and reveal an unexpected link between new strategies for cancer chemotherapy and the treatment of axonopathies.
Asunto(s)
Axones/metabolismo , Degeneración Nerviosa/metabolismo , Mononucleótido de Nicotinamida/metabolismo , Traumatismos de los Nervios Periféricos/metabolismo , Amidohidrolasas/farmacología , Animales , Axones/patología , Proteínas Bacterianas/farmacología , Ratones , Degeneración Nerviosa/tratamiento farmacológico , Degeneración Nerviosa/genética , Degeneración Nerviosa/patología , Nicotinamida-Nucleótido Adenililtransferasa/metabolismo , Traumatismos de los Nervios Periféricos/tratamiento farmacológico , Traumatismos de los Nervios Periféricos/genética , Traumatismos de los Nervios Periféricos/patologíaRESUMEN
OBJECTIVE: To test the hypothesis that greater exposure to smoking in films is associated with trying smoking among adolescents. DESIGN: Cross sectional survey of 4919 schoolchildren aged 9-15 years, and assessment of occurrence of smoking in 601 films. SETTING: Randomly selected middle schools in Vermont and New Hampshire, USA. MAIN OUTCOME MEASURE: Number of schoolchildren who had ever tried smoking a cigarette. RESULTS: The films contained a median of 5 (interquartile range 1-12) occurrences of smoking. The typical adolescent had seen 17 of 50 films listed. Exposure to smoking in films varied widely: median 91 (49-152) occurrences. The prevalence of ever trying smoking increased with higher categories of exposure: 4.9% among students who saw 0-50 occurrences of smoking, 13.7% for 51-100 occurrences, 22.1% for 101-150, and 31.3% for >150. The association remained significant after adjustment for age; sex; school performance; school; parents' education; smoking by friend, sibling, or parent; and receptivity to tobacco promotions. The adjusted odds ratios of ever trying smoking for students in the higher categories of exposure, compared with students exposed to 0-50 occurrences of smoking in films, were 1.7 (95% confidence interval 1.2 to 2.4), 2.4 (1.7 to 3.4), and 2.7 (2.0 to 3.8). These odds ratios were not substantially affected by adjustment for parenting style or for personality traits of the adolescent. CONCLUSION: In this sample of adolescents there was a strong, direct, and independent association between seeing tobacco use in films and trying cigarettes, a finding that supports the hypothesis that smoking in films has a role in the initiation of smoking in adolescents.
Asunto(s)
Conducta del Adolescente/psicología , Conducta Imitativa , Películas Cinematográficas , Fumar/epidemiología , Adolescente , Factores de Edad , Niño , Estudios Transversales , Femenino , Humanos , Masculino , New Hampshire/epidemiología , Oportunidad Relativa , Prevalencia , Psicometría , Factores de Riesgo , Fumar/psicología , Medio Social , Televisión , Vermont/epidemiologíaRESUMEN
BACKGROUND: The appearance of a cigarette brand in a cinema film gives the brand a certain distinction through its association with the characters and general tone of the film. Through the worldwide distribution of films, brands are promoted globally. We assessed the tobacco-brand appearances in a 10-year sample of contemporary films. METHODS: We viewed the contents of the top 25 US box-office films for each year of release, from 1988 to 1997 (250 films in total). We compared the prevalence of brand appearances for films produced before a voluntary ban on paid product placement by the tobacco industry (1988-90) with films produced after the ban (1991-97). Tobacco-brand appearance was defined as the screen appearance of a brand name, logo, or identifiable trademark on products or product packaging, billboards, store-front advertising, or tobacco promotional items. We defined actor endorsement of a brand as the display of a brand while being handled or used by an actor. FINDINGS: More than 85% of the films contained tobacco use. Tobacco brands appeared in 70 (28%) films. Brand appearances were as common in films suitable for adolescent audiences as they were in films for adult audiences (32 vs 35%), and were also present in 20% of those rated for children. Prevalence of brand appearance did not change overall in relation to the ban. However, there was a striking increase in the type of brand appearance depicted, with actor endorsement increasing from 1% of films before the ban to 11% after. Four US cigarette brands accounted for 80% of brand appearances. Revenues outside the USA accounted for 49% of total revenues for these films, indicating a large international audience. INTERPRETATION: Tobacco-brand appearances are common in films and are becoming increasingly endorsed by actors. The most highly advertised US cigarette brands account for most brand appearances, which suggests an advertising motive to this practice.
Asunto(s)
Publicidad/métodos , Películas Cinematográficas/estadística & datos numéricos , Nicotiana , Plantas Tóxicas , Femenino , Humanos , Masculino , Fumar/economía , Factores de Tiempo , Industria del Tabaco/economía , Industria del Tabaco/legislación & jurisprudenciaRESUMEN
OBJECTIVE: To assess the relation between adolescents' favourite movie stars, the portrayal of tobacco use by those stars in contemporary motion pictures, and adolescent smoking. DESIGN AND SETTING: 632 students (sixth to 12th grade, ages 10-19 years) from five rural New England public schools completed a voluntary, self administered survey in October 1996. The survey assessed tobacco use, other variables associated with adolescent smoking, and favourite movie star. In addition, tobacco use by 43 selected movie stars was measured in films between 1994 and 1996. OUTCOME MEASURES: Students were categorised into an ordinal five point index (tobacco status) based on their smoking behaviour and their smoking susceptibility: non-susceptible never smokers, susceptible never smokers, non-current experimenters, current experimenters, and smokers. We determined the adjusted cumulative odds of having advanced smoking status based on the amount of on-screen tobacco use by their favourite film star. RESULTS: Of the 43 stars, 65% used tobacco at least once, and 42% portrayed smoking as an essential character trait in one or more films. Stars who smoked more than twice in a film were considered smokers. For adolescents whose favourite stars smoked in only one film, the odds of being higher on the smoking index was 0.78 (95% confidence interval (CI) 0.53 to 1.15). For adolescents whose favourite stars smoked in two films, the odds of being higher on the smoking index was 1.5 (95% CI 1.01 to 2.32). For adolescents whose favourite stars smoked in three or more films (Leonardo DiCaprio, Sharon Stone, John Travolta), the odds of being higher on the smoking index was 3.1 (95% CI 1.34 to 7.12). Among never smokers (n = 281), those who chose stars who were smokers in three or more films were much more likely to have favourable attitudes toward smoking (adjusted odds ratio 16.2, 95% CI 2.3 to 112). CONCLUSIONS: Adolescents who choose movie stars who use tobacco on-screen are significantly more likely to have an advanced smoking status and more favourable attitudes toward smoking than adolescents who choose non-smoking stars. This finding supports the proposition that the portrayal of tobacco use in contemporary motion pictures, particularly by stars who are admired by adolescents, contributes to adolescent smoking.