Regulation of iron homeostasis and cancer development

Iron is one of the essential trace elements in human body,which plays a critical role in electron respiratory chain,DNA synthesis,and oxygen utilization.The iron content in adult body is about 40 mg/kg[1].When iron content in human body decreases,the normal physiological functions are affected,which causes series of iron deficiency diseases,such as iron deficiency anemia.Iron deficiency is a common nutritional deficiency that affects over 2 billion people worldwide[2].Iron deficiency leads to immune,neurological,respiratory,and other disorders.There is a dynamic balance of iron metabolism in human body,which includes three main processes:iron uptake,storage,and output.It is absorbed by small intestinal epithelial cells,stored in red blood cells,liver,and muscle fibers,and exported by excrement or shedding of small intestinal epithelial cells.

Centrosome and vascular microenvironmental homeostasis

The homeostasis of vascular microenvironment is essential to maintain the normal vascular structure and function,while its disorder leads to vascular dysfunction,and cardiovascular and cerebrovascular diseases.Centrosome is an important organelle existing in mammalian cells as well as the microtubule organizing center,playing an important role in maintaining vascular structure and homeostasis.This study reviewed the role of centrosome in the regulation of vascular microenvironmental homeostasis.Centrosomal proteins intricately regulate microtubule dynamics and stabilization,and diverse microtubule-relatived cellular activities,including the division,polarization and directional migration of vascular endothelial cells,smooth muscle cells and other types of cells.In addition,primary cilia formed by centrosome are essential in vascular microenvironment.Tumor endothelial cells usually acquire excess centrosomes,and excess centrosomes are regulated by several angiogenic factors.Therefore,uncovering the detailed molecular mechanisms underlying centrosome affecting vascular microenvironmental homeostasis are needed for the treatment of cardiovascular and cerebrovascular diseases.

Targeting mitochondrial protein transport system:a promising treatment strategy for heart failure?

Heart failure(HF)is a severe condition in which the heart is unable to pump enough blood to maintain the normal demand of body for oxygen and nutrients[1].Heart failure is also the common end result of several heart diseases and the leading cause of death of cardiovascular diseases(CVDs)[2].There is still no effective method for the diagnosis of heart failure,and its diagnosis is made by a comprehensive history,symptoms and objective examination[3].The therapeutic drugs for heart failure mainly include diuretics,RAAS inhibitors,β-receptor antagonists and antiplatelet drugs,etc.,which can improve the symptoms of heart failure patients by increasing urination,reducing myocardial remodeling,inhibiting sympathetic nerve activity and relieving blood embolism,delaying the disease progression and reducing mortality[4].However,there is still a lack of effective early diagnostic markers and therapeutic drugs for heart failure.

Redox-dependent regulation of end-binding protein 1 activity by glutathionylation

Cytoskeletal proteins are susceptible to glutathionylation under oxidizing conditions,and oxidative damage has been implicated in several neurodegenerative diseases.End-binding protein 1(EB1)is a master regulator of microtubule plus-end tracking proteins(+TIPs)and is critically involved in the control of microtubule dynamics and cellular processes.However,the impact of glutathionylation on EB1 functions remains unknown.Here we reveal that glutathionylation is important for controlling EB1 activity and protecting EB1 from irreversible oxidation.In vitro biochemical and cellular assays reveal that EB1 is glutathionylated.Diamide,a mild oxidizing reagent,reduces EB1 comet number and length in cells,indicating the impairment of microtubule dynamics.Three cysteine residues of EB1 are glutathionylated,with mutations of these three cysteines to serines attenuating microtubule dynamics but buffering diamide-induced decrease in microtubule dynamics.In addition,glutaredoxin 1(Grx1)deglutathionylates EB1,and Grx1 depletion suppresses microtubule dynamics and leads to defects in cell division orientation and cell migration,suggesting a critical role of Grx1-mediated deglutathionylation in maintaining EB1 activity.Collectively,these data reveal that EB1 glutathionylation is an important protective mechanism for the regulation of microtubule dynamics and microtubule-based cellular activities.

A cilium-independent role for intraflagellar transport 88 in regulating angiogenesis

Endothelial cilia are microtubule-based hair-like protrusions in the lumen of blood vessels that function as fluid mechanosensors to regulate vascular hemodynamics. However, the functions of endothelial cilia in vascular development remain controversial. In this study, depletion of several key proteins responsible for ciliogenesis allows us to identify a cilium-independent role for intraflagellar transport 88(IFT88) in mammalian angiogenesis. Disruption of primary cilia by heat shock does not affect the angiogenic process. However, depletion of IFT88 significantly inhibits angiogenesis both in vitro and in vivo. IFT88 mediates angiogenesis by regulating the migration, polarization, proliferation, and oriented division of vascular endothelial cells. Further mechanistic studies demonstrate that IFT88 interacts with c-tubulin and microtubule plus-end tracking proteins and promotes microtubule stability. Our findings indicate that IFT88 regulates angiogenesis through its actions in microtubule-based cellular processes, independent of its role in ciliogenesis.