Regulation of GTP-binding Protein (Galpha s) Expression in Human Myometrial Cells A ROLE FOR TUMOR NECROSIS FACTOR IN MODULATING G s PROMOTER ACETYLATION BY TRANSCRIPTIONAL COMPLEXES

The onset of parturition is associated with a number of proinflammatory mediators that are themselves regulated by the nuclear factor κB (NF-κB) family of transcription factors. In this context, we previously reported that the RelA NF-κB subunit represses transcription and mRNA expression of the proquiescent Gαs gene in human myometrial cells following stimulation with the proinflammatory cytokine TNF. In the present study, we initially defined the functional consequence of this on myometrial contractility. Here we show that, contrary to our initial expectations, TNF did not induce myometrial contractility but did inhibit the relaxation produced by the histone deacetylase inhibitor trichostatin A, an effect that in turn was abolished by the NF-κB inhibitor N4-[2-(4-phenoxyphenyl)ethyl]-4,6-quinazolinediamine. This result suggested a role for TNF in regulating Gαs expression via activating NF-κB and modifying histone acetylation associated with the promoter region of the gene. In this context, we show that the −837 to −618 region of the endogenous Gαs promoter is occupied by cAMP-response element-binding protein (CREB), Egr-1, and Sp1 transcription factors and that CREB-binding protein (CBP) transcriptional complexes form within this region where they induce histone acetylation, resulting in increased Gαs expression. TNF, acting via NF-κB, did not change the levels of CREB, Sp1, or Egr-1 binding to the Gαs promoter, but it induced a significant reduction in the level of CBP. This was associated with increased levels of histone deacetylase-1 and surprisingly an increase in H4K8 acetylation. The latter is discussed herein

Trends of weight gain and prevalence of overweight and obesity from birth to three years of age

Objective: To examine the changes in children’s weight-for-height at six monthly intervals between birth and three years old (3yo) from different counties across Chile and to determine if children had overweight or obesity, and if so, whether it was a transient or persistent change. Subjects and methods: Longitudinal data were obtained from routine medical check-ups and 8,373 children were selected from nine counties in Chile through a non-randomised sample design. Weight-for-height z-scores (WHZ) were generated and categorized as wasted, normal, overweight, and obese using WHO standards. Repeated-measures ANOVA were used to analyse the changes in WHZ over the seven measurements as well as based on having normal, overweight, or obese WHZ at 3yo. The number of times having overweight or obesity was counted (from 0 to 7 times). The timing of having overweight and obesity was computed as well as all combinations of the patterns. Results: Mean WHZ significantly increased up to 18 months of age and declined thereafter (p « 0.001). Overall mean WHZ was 0.743, prevalence of overweight 31.2% and prevalence of obesity 10.0%. Children categorised with overweight or obesity at 3yo showed significantly higher and sustained pattern of weight gain compared with children with normal WHZ. Once a child had overweight or obesity they tended to remain with it and did not return to a weight-for-height in the normal range. Conclusion: The increasing prevalence of overweight and obesity in Chilean children is of concern. There is a need for greater healthcare promotion and prevention of this disease from infancy