Salubrinal promotes phospho-eIF2α-dependent activation of UPR leading to autophagy-mediated attenuation of iron-induced insulin resistance.

Identification of new mechanisms mediating insulin sensitivity is important to allow validation of corresponding therapeutic targets. In this study, we first used a cellular model of skeletal muscle cell iron overload and found that endoplasmic reticulum (ER) stress and insulin resistance occurred after iron treatment. Insulin sensitivity was assessed using cells engineered to express an Akt biosensor, based on nuclear FoxO localization, as well as western blotting for insulin signaling proteins.

A crosstalk between hepcidin and IRE/IRP pathways controls ferroportin expression and determines serum iron levels in mice.

The iron hormone hepcidin is transcriptionally activated by iron or inflammation via distinct, partially overlapping pathways. We addressed how iron affects inflammatory hepcidin levels and the ensuing hypoferremic response. Dietary iron overload did not mitigate hepcidin induction in lipopolysaccharide (LPS)-treated wild type mice but prevented effective inflammatory hypoferremia.

The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages.

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects.

Interventions facilitating access to perinatal care for migrant women without medical insurance: A scoping review protocol.

Introduction: Inadequate pregnancy monitoring for pregnant migrant women without medical insurance (PMWMI) exposes them to severe complications during childbirth and consequences for the health of their child (e.g. preterm delivery, low birth weight, etc.

Iron overload inhibits BMP/SMAD and IL-6/STAT3 signaling to hepcidin in cultured hepatocytes.

Hepcidin is a peptide hormone that targets the iron exporter ferroportin, thereby limiting iron entry into the bloodstream. It is generated in hepatocytes mainly in response to increased body iron stores or inflammatory cues. Iron stimulates expression of bone morphogenetic protein 6 (BMP6) from liver sinusoidal endothelial cells, which in turn binds to BMP receptors on hepatocytes and induces the SMAD signaling cascade for transcriptional activation of the hepcidin-encoding HAMP mRNA.

Iron Reshapes the Gut Microbiome and Host Metabolism.

Compelling studies have established that the gut microbiome is a modifier of metabolic health. Changes in the composition of the gut microbiome are influenced by genetics and the environment, including diet. Iron is a potential node of crosstalk between the host-microbe relationship and metabolic disease.

[Complicaciones trombóticas en COVID-19 grave: enfoque en tromboembolia venosa, tromboprofilaxis y anticoagulación].

La enfermedad grave por coronavirus 2019 (COVID-19) está causada por el Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) y predispone a complicaciones trombóticas. En esta revisión se aborda de manera práctica la estrecha relación entre la tromboembolia venosa y la COVID-19, enfatizando aspectos epidemiológicos, factores de riesgo y tromboprofilaxis, así como potenciales opciones de anticoagulación. Actualmente la evidencia científica es muy escasa, pero día a día seguimos aprendiendo, estando atentos a cambios novedosos y dinámicos en esta enfermedad infecciosa e inmunotrombótica emergente.

Regulatory Connections between Iron and Glucose Metabolism.

Iron is essential for energy metabolism, and states of iron deficiency or excess are detrimental for organisms and cells. Therefore, iron and carbohydrate metabolism are tightly regulated. Serum iron and glucose levels are subjected to hormonal regulation by hepcidin and insulin, respectively.

Basics and principles of cellular and systemic iron homeostasis.

Iron is a constituent of many metalloproteins involved in vital metabolic functions. While adequate iron supply is critical for health, accumulation of excess iron promotes oxidative stress and causes tissue injury and disease. Therefore, iron homeostasis needs to be tightly controlled.

Transferrin receptor 1 controls systemic iron homeostasis by fine-tuning hepcidin expression to hepatocellular iron load.

Transferrin receptor 1 (Tfr1) mediates uptake of circulating transferrin-bound iron to developing erythroid cells and other cell types. Its critical physiological function is highlighted by the embryonic lethal phenotype of Tfr1-knockout (Tfrc) mice and the pathologies of several tissue-specific knockouts. We generated Tfrc mice bearing hepatocyte-specific ablation of Tfr1 to explore implications in hepatocellular and systemic iron homeostasis.

Differences in activation of mouse hepcidin by dietary iron and parenterally administered iron dextran: compartmentalization is critical for iron sensing.

The iron regulatory hormone hepcidin responds to both oral and parenteral iron. Here, we hypothesized that the diverse iron trafficking routes may affect the dynamics and kinetics of the hepcidin activation pathway. To address this, C57BL/6 mice were administered an iron-enriched diet or injected i.

Mechanisms of mammalian iron homeostasis.

Iron is vital for almost all organisms because of its ability to donate and accept electrons with relative ease. It serves as a cofactor for many proteins and enzymes necessary for oxygen and energy metabolism, as well as for several other essential processes. Mammalian cells utilize multiple mechanisms to acquire iron.

Immuno-characterization of the switch of peptide elongation factors eEF1A-1/EF-1alpha and eEF1A-2/S1 in the central nervous system during mouse development.

During early postnatal development, a switch occurs between eEF1A-1/EF-1alpha and eEF1A-2/S1, homologous peptide elongation factors, in brain, heart, and skeletal muscle; eEF1A-2/S1 becomes the major form expressed in maturity. By immunofluorescent labeling, we detected both homologues in the developing brains of wild-type and wasted mutant mice, carrying a deletion in the eEF1A-2/S1 gene; we found that brain expression of eEF1A-2/S1 protein is restricted to mature, terminally differentiated neurons, and coincides with the disappearance of eEF1A-1/EF-1alpha 20 days after birth. Furthermore, no elongation factor 1A is present in wasted mutant mice neurons following the developmental switch, indicating that the genetic regulation silencing eEF1A-1/EF-1alpha is still functional.

hMad4, c-Myc endogenous inhibitor, induces a replicative senescence-like state when overexpressed in human fibroblasts.

Mad family proteins have an antagonistic action on Myc-dependent cell proliferation and transformation. We isolated a human cDNA clone, human Mad4 (hMad4), encoding a polypeptide of 209 amino acid residues, exhibiting 90% identity with mouse Mad4. Northern blot analysis shows that hMad4 probe hybridizes to a 3.

Development-dependent disappearance of caspase-3 in skeletal muscle is post-transcriptionally regulated.

Caspase-3, a major player in apoptosis, engages apoptosis-activated cells into an irreversible pathway leading to cell death. In this article, we report that caspase-3 protein is absent from rat and mouse adult skeletal muscles, despite the abundant presence of its mRNA. During skeletal muscle development, caspase-3 protein is present in neonatal animals, but its expression gradually decreases, and disappears completely by 1 month of age, when there is still abundant caspase-3 mRNA.

Castration-induced apoptosis in the rat ventral prostate is associated with increased expression of genes encoding insulin-like growth factor binding proteins 2,3,4 and 5.

Insulin-like growth factor binding proteins (IGFBPs) have recently been demonstrated to act as regulators of apoptosis in vitro in both prostate and breast cancer cell lines. We show here that gene expression of IGFBP-2,-3,-4 and -5 increase rapidly in the rat ventral prostate following castration. Increases in IGFBP mRNA levels were detectable by Northern blotting by 6 hours and reached 5 to 10 fold of control levels at 72 hours after castration.

Antiproliferative action of vitamin D-related compounds and insulin-like growth factor-binding protein 5 accumulation.

Background And Purpose: Vitamin D-related compounds can inhibit cancer cell growth, but the biologic mechanism of this inhibition remains to be determined. We investigated the possibility that these compounds interfere with the activity of insulin-like growth factors. Such activity can be suppressed or otherwise modulated by specific insulin-like growth factor-binding proteins.