Glucose-induced posttranslational activation of protein phosphatases PP2A and PP1 in yeast

The protein phosphatases PP2A and PP1 are major regulators of a variety of cellular processes in yeast and other eukaryotes. Here, we reveal that both enzymes are direct targets of glucose sensing. Addition of glucose to glucose-deprived yeast cells triggered rapid posttranslational activation of both PP2A and PP1. Glucose activation of PP2A is controlled by regulatory subunits Rts1, Cdc55, Rrd1 and Rrd2. It is associated with rapid carboxymethylation of the catalytic subunits, which is necessary but not sufficient for activation. Glucose activation of PP1 was fully dependent on regulatory subunits Reg1 and Shp1. Absence of Gac1, Glc8, Reg2 or Red1 partially reduced activation while Pig1 and Pig2 inhibited activation. Full activation of PP2A and PP1 was also dependent on subunits classically considered to belong to the other phosphatase. PP2A activation was dependent on PP1 subunits Reg1 and Shp1 while PP1 activation was dependent on PP2A subunit Rts1. Rts1 interacted with both Pph21 and Glc7 under different conditions and these interactions were Reg1 dependent. Reg1-Glc7 interaction is responsible for PP1 involvement in the main glucose repression pathway and we show that deletion of Shp1 also causes strong derepression of the invertase gene SUC2. Deletion of the PP2A subunits Pph21 and Pph22, Rrd1 and Rrd2, specifically enhanced the derepression level of SUC2, indicating that PP2A counteracts SUC2 derepression. Interestingly, the effect of the regulatory subunit Rts1 was consistent with its role as a subunit of both PP2A and PP1, affecting derepression and repression of SUC2, respectively. We also show that abolished phosphatase activation, except by reg1Δ, does not completely block Snf1 dephosphorylation after addition of glucose. Finally, we show that glucose activation of the cAMP-PKA (protein kinase A) pathway is required for glucose activation of both PP2A and PP1. Our results provide novel insight into the complex regulatory role of these two major protein phosphatases in glucose regulation

Exercise and bone health across the lifespan

With ageing, bone tissue undergoes significant compositional, architectural and metabolic alterations potentially leading to osteoporosis. Osteoporosis is the most prevalent bone disorder, which is characterised by progressive bone weakening and an increased risk of fragility fractures. Although this metabolic disease is conventionally associated with ageing and menopause, the predisposing factors are thought to be established during childhood and adolescence. In light of this, exercise interventions implemented during maturation are likely to be highly beneficial as part of a long-term strategy to maximise peak bone mass and hence delay the onset of age- or menopause-related osteoporosis. This notion is supported by data on exercise interventions implemented during childhood and adolescence, which confirmed that weight-bearing activity, particularly if undertaken during peripubertal development, is capable of generating a significant osteogenic response leading to bone anabolism. Recent work on human ageing and epigenetics suggests that undertaking exercise after the fourth decade of life is still important, given the anti-ageing effect and health benefits provided, potentially occurring via a delay in telomere shortening and modification of DNA methylation patterns associated with ageing. Exercise is among the primary modifiable factors capable of influencing bone health by preserving bone mass and strength, preventing the death of bone cells and anti-ageing action provided

Obesidade e adipocinas inflamatórias: implicações práticas para a prescrição de exercício Obesity and inflammatory adipokines: practical implications for exercise prescription

A obesidade é uma doença complexa de etiologia multifacetada, com sua própria fisiopatologia, comorbidades e capacidades desabilitantes. Aceitar a obesidade como uma doença é fundamental para o seu tratamento. Atualmente, o tecido adiposo é um dos principais focos das pesquisas em obesidade, devido a uma revolução no entendimento da função biológica desse tecido desde a última década. Já está muito claro que o tecido adiposo branco secreta múltiplos peptídeos bioativos, denominados adipocinas (proteínas sintetizadas e secretadas pelo tecido adiposo). Dessa forma, o objetivo deste trabalho de revisão foi investigar a relação entre obesidade e adipocinas inflamatórias, buscando discutir o papel do exercício físico no tratamento dessa patologia. Os resultados demonstram que uma das mais importantes descobertas das pesquisas recentes em obesidade é o conceito de que ela é caracterizada por uma inflamação crônica. Dentre todas as adipocinas, sem dúvida, a IL-6, o TNF-&#945;, a leptina (pró-inflamatórias) e a adiponectina (anti-inflamatória) vêm recebendo atenção especial da literatura especializada. O aumento da concentração dessas adipocinas promove grande impacto em diversas funções corporais que estão fortemente correlacionadas com doenças cardiovasculares. Uma vez que a obesidade é considerada uma doença inflamatória e o exercício físico modula de forma direta tais processos, é essencial que tenhamos como um dos objetivos principais de nossos programas de exercícios físicos a melhora da resposta inflamatória de obesos.<br>Obesity is a complex disease with a multifaceted etiology with its own physiopathology, co-morbidities and disabiliting capacities. It is crucial that obesity is acknowledged as a disease in order to treat it. Nowadays, the adipose tissue is the main focus of obesity research due to the improvement in the last decade on biological function of this tissue. It is now clear that white adipose tissue release a large amount of bioactive peptides called adipokines (which are proteins synthesized and released by adipose tissue). Thus, the aim of this review was to investigate the relationship between obesity and inflammatory adipokines, trying to discuss the role of physical exercise in the treatment of this pathology. The results have shown that one of the most important recent discoveries is the concept that obesity is characterized by a chronic inflammation state. Among all adipokines, IL-6, TNF- &#945;, leptin (pro-inflammatory) and adiponectin (anti-inflammatory), have received special attention from the specialized literature. High concentration of these adipokines promotes impact in several body functions, which is strongly linked with cardiovascular diseases. Since obesity is considered an inflammatory disease, and exercise directly modulates this process, it is essential that one of the main aims of exercise therapies is the improvement of the inflammatory response of obese individuals