STIM1/Orai1-mediated store-operated Ca2+ entry: the tip of the iceberg

Highly efficient mechanisms regulate intracellular calcium (Ca2+) levels. The recent discovery of new components linking intracellular Ca2+ stores to plasma membrane Ca2+ entry channels has brought new insight into the understanding of Ca2+ homeostasis. Stromal interaction molecule 1 (STIM1) was identified as a Ca2+ sensor essential for Ca2+ store depletion-triggered Ca2+ influx. Orai1 was recognized as being an essential component for the Ca2+ release-activated Ca2+ (CRAC) channel. Together, these proteins participate in store-operated Ca2+ channel function. Defective regulation of intracellular Ca2+ is a hallmark of several diseases. In this review, we focus on Ca2+ regulation by the STIM1/Orai1 pathway and review evidence that implicates STIM1/Orai1 in several pathological conditions including cardiovascular and pulmonary diseases, among others

IKKβ targeting reduces KRAS-induced lung cancer angiogenesis in vitro and in vivo: A potential anti-angiogenic therapeutic target

Objectives: The ability of tumor cells to drive angiogenesis is an important cancer hallmark that positively correlates with metastatic potential and poor prognosis. Therefore, targeting angiogenesis is a rational therapeutic approach and dissecting proangiogenic pathways is important, particularly for malignancies driven by oncogenic KRAS, which are widespread and lack effective targeted therapies. Based on published studies showing that oncogenic RAS promotes angiogenesis by upregulating the proangiogenic NF-κB target genes IL-8 and VEGF, that NF-κB activation by KRAS requires the IKKβ kinase, and that targeting IKKβ reduces KRAS-induced lung tumor growth in vivo, but has limited effects on cell growth in vitro, we hypothesized that IKKβ targeting would reduce lung tumor growth by inhibiting KRAS-induced angiogenesis. Materials and methods: To test this hypothesis, we targeted IKKβ in KRAS-mutant lung cancer cell lines either by siRNA-mediated transfection or by treatment with Compound A (CmpdA), a highly specific IKKβ inhibitor, and used in vitro and in vivo assays to evaluate angiogenesis. Results and conclusions: Both pharmacological and siRNA-mediated IKKβ targeting in lung cells reduced expression and secretion of NF-κB-regulated proangiogenic factors IL-8 and VEGF. Moreover, conditioned media from IKKβ-targeted lung cells reduced human umbilical vein endothelial cell (HUVEC) migration, invasion and tube formation in vitro. Furthermore, siRNA-mediated IKKβ inhibition reduced xenograft tumor growth and vascularity in vivo. Finally, IKKβ inhibition also affects endothelial cell function in a cancer-independent manner, as IKKβ inhibition reduced pathological retinal angiogenesis in a mouse model of oxygen-induced retinopathy. Taken together, these results provide a novel mechanistic understanding of how the IKKβ pathway affects human lung tumorigenesis, indicating that IKKβ promotes KRAS-induced angiogenesis both by cancer cell-intrinsic and cancer cell-independent mechanisms, which strongly suggests IKKβ inhibition as a promising antiangiogenic approach to be explored for KRAS-induced lung cancer therapy

"Plantar pro gasto": a importância do autoconsumo entre famílias de agricultores do Rio Grande do Sul.

O artigo discute a valoração e importância da produção para o autoconsumo na reprodução social das unidades familiares e caracteriza os alimentos autoconsumidos. Vale-se da pesquisa "Agricultura Familiar, Desenvolvimento Local e Pluriatividade" (UFRGS/UFPel/ CNPq-2003) que propiciou a formação de um banco de dados com informações sobre a dinâmica da agricultura familiar em quatro regiões distintas da geografia gaúcha, suas fontes e tipos de renda, entre estas o autoconsumo. Trazer este debate significa retomar um tema pouco discutido até então, e que, embora marginalizado ou considerado sem importância, desenvolve importante papel como renda não monetária, fortalece a segurança alimentar e adentra esferas da sociabilidade e identidade social. Além da introdução, apresenta-se o papel do autoconsumo na agricultura familiar, o cálculo da produção para o autoconsumo, discussão dos objetivos e resultados, e considerações finais. Os resultados demonstram que a produção para o autoconsumo é uma estratégia recorrente pelas unidades familiares e se diferencia de acordo com a dinâmica da agricultura familiar. Diferença esta expressa em valores relativos (%) e no número de estabelecimentos pertencentes a estratos diferenciados de autoconsumo, e pouco nos tipos de alimentos produzidos para este fim, observando-se uma homogeneidade dos hábitos alimentares