Plant hormones: metabolism, signaling and crosstalk

Plants synthesize various hormones in response to environmental cues and developmental signals to ensure their proper growth and development.Elucidation of the molecular mechanisms by which plant hormones control growth and development contributes to our understanding of fundamental plant biology and provides tools to improve crops.Because of their critical roles in plant growth and development, plant hormones have been studied extensively since the early days of plant biology.     

Endothelial connexin-integrin crosstalk in vascular inflammation

Cardiovascular diseases including blood vessel disorders represent a major cause of death globally. The essential roles played by local and systemic vascular inflammation in the pathogenesis of cardiovascular diseases have been increasingly recognized. Vascular inflammation triggers the aberrant activation of endothelial cells, which leads to the functional and structural abnormalities in vascular vessels. In addition to humoral mediators such as pro-inflammatory cytokines and prostaglandins, the alteration of physical and mechanical microenvironment – including vascular stiffness and shear stress – modify the gene expression profiles and metabolic profiles of endothelial cells via mechano-transduction pathways, thereby contributing to the pathogenesis of vessel disorders. Notably, connexins and integrins crosstalk each other in response to the mechanical stress, and, thereby, play an important role in regulating the mechano-transduction of endothelial cells. Here, we provide an overview on how the inter-play between connexins and integrins in endothelial cells unfold during the mechano-transduction in vascular inflammation.     

铁代谢与蛋白质泛素化．降解调控研究进展

铁元素为几乎所有的生命体所必需,维持铁代谢稳态对机体的正常功能至关重要。铁代谢紊乱与人类多种疾病的发生和发展有关。已知铁代谢稳态受到一系列参与铁代谢环节的关键蛋白质,如IRP2等的精确调节。这些重要蛋白质的稳定性、生理活性的动态变化及其协调作用是细胞维持铁代谢平衡的分子基础。除了转录和转录后水平的调控,泛素化等翻译后修饰方式和蛋白质降解是细胞精确调控参与铁代谢的蛋白质的水平及功能普遍而有效的方式之一;同时,细胞的铁代谢状态也影响细胞内参与泛素化等翻译后修饰途径的酶类的活性和稳定性,从而在铁代谢和蛋白质修饰．降解途径之间形成反馈机制,实时和动态地完成对细胞内铁代谢水平的精确调控。就相关领域的最新进展作简要综述。     

The interplay between inflammation and metabolism in rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone that lead to joint destruction. The autoimmune process in RA depends on the activation of immune cells, which use intracellular kinases to respond to external stimuli such as cytokines, immune complexes, and antigens. An intricate cytokine network participates in inflammation and in perpetuation of disease by positive feedback loops promoting systemic disorder. The widespread systemic effects mediated by pro-inflammatory cytokines in RA impact on metabolism and in particular in lymphocyte metabolism. Moreover, RA pathobiology seems to share some common pathways with atherosclerosis, including endothelial dysfunction that is related to underlying chronic inflammation. The extent of the metabolic changes and the types of metabolites seen may be good markers of cytokine-mediated inflammatory processes in RA. Altered metabolic fingerprints may be useful in predicting the development of RA in patients with early arthritis as well as in the evaluation of the treatment response. Evidence supports the role of metabolomic analysis as a novel and nontargeted approach for identifying potential biomarkers and for improving the clinical and therapeutical management of patients with chronic inflammatory diseases. Here, we review the metabolic changes occurring in the pathogenesis of RA as well as the implication of the metabolic features in the treatment response.     

Self-eating and self-killing: crosstalk between autophagy and apoptosis

The functional relationship between apoptosis ('self-killing') and autophagy ('self-eating') is complex in the sense that, under certain circumstances, autophagy constitutes a stress adaptation that avoids cell death (and suppresses apoptosis), whereas in other cellular settings, it constitutes an alternative cell-death pathway. Autophagy and apoptosis may be triggered by common upstream signals, and sometimes this results in combined autophagy and apoptosis; in other instances, the cell switches between the two responses in a mutually exclusive manner. On a molecular level, this means that the apoptotic and autophagic response machineries share common pathways that either link or polarize the cellular responses.     

Small leucine-rich proteoglycans orchestrate receptor crosstalk during inflammation

Inflammation is not only a defensive mechanism against microbial invasion, but also frequently represents a critical response to tissue injury under sterile conditions. It is now well established that tissue injury leads to the release of endogenous molecules of intra- and extracellular origin acting as damage-associated molecular patterns (DAMPs). The small leucine-rich proteoglycans (SLRPs) can act as powerful DAMPs following their proteolytical release from the extracellular matrix. Recent investigations of SLRP signaling networks revealed new levels of complexity, showing that SLRPs can cluster different types of receptors and orchestrate a host of downstream signaling events. This review will summarize the evidence for the multifunctional proinflammatory signaling properties of the two archetypal SLRPs, biglycan and decorin. These secreted proteoglycans link the innate to the adaptive immune response and operate in a broad biological context, encompassing microbial defense, tumor growth and autoimmunity.     

Hypoxia-inducible factor 1: Regulator of mitochondrial metabolism and mediator of ischemic preconditioning

Hypoxia-inducible factor 1 (HIF-1) mediates adaptive responses to reduced oxygen availability by regulating gene expression. A critical cell-autonomous adaptive response to chronic hypoxia controlled by HIF-1 is reduced mitochondrial mass and/or metabolism. Exposure of HIF-1-deficient fibroblasts to chronic hypoxia results in cell death due to excessive levels of reactive oxygen species (ROS). HIF-1 reduces ROS production under hypoxic conditions by multiple mechanisms including: a subunit switch in cytochrome c oxidase from the COX4-1 to COX4-2 regulatory subunit that increases the efficiency of complex IV; induction of pyruvate dehydrogenase kinase 1, which shunts pyruvate away from the mitochondria; induction of BNIP3, which triggers mitochondrial selective autophagy; and induction of microRNA-210, which blocks assembly of Fe/S clusters that are required for oxidative phosphorylation. HIF-1 is also required for ischemic preconditioning and this effect may be due in part to its induction of CD73, the enzyme that produces adenosine. HIF-1-dependent regulation of mitochondrial metabolism may also contribute to the protective effects of ischemic preconditioning. This article is part of a Special Issue entitled: Mitochondria and Cardioprotection.     

Sphingolipids: regulators of crosstalk between apoptosis and autophagy

Apoptosis and autophagy are two evolutionarily conserved processes that maintain homeostasis during stress. Although the two pathways utilize fundamentally distinct machinery, apoptosis and autophagy are highly interconnected and share many key regulators. The crosstalk between apoptosis and autophagy is complex, as autophagy can function to promote cell survival or cell death under various cellular conditions. The molecular mechanisms of crosstalk are beginning to be elucidated and have critical implications for the treatment of various diseases, such as cancer. Sphingolipids are a class of bioactive lipids that mediate many key cellular processes, including apoptosis and autophagy. By targeting several of the shared regulators, sphingolipid metabolites differentially regulate the induction of apoptosis and autophagy. Importantly, individual sphingolipid species appear to “switch” autophagy toward cell survival (e.g., sphingosine-1-phosphate) or cell death (e.g., ceramide, gangliosides). This review assesses the current understanding of sphingolipid-induced apoptosis and autophagy to address how sphingolipids mediate the “switch” between the cell survival and cell death. As sphingolipid metabolism is frequently dysregulated in cancer, sphingolipid-modulating agents, or sphingomimetics, have emerged as a novel chemotherapeutic strategy. Ultimately, a greater understanding of sphingolipid-mediated crosstalk between apoptosis and autophagy may be critical for enhancing the chemotherapeutic efficacy of these agents.     

A time to fast,a time to feast: The crosstalk between metabolism and the circadian clock

The cyclic environmental conditions brought about by the 24 h rotation of the earth have allowed the evolution of endogenous circadian clocks that control the temporal alignment of behaviour and physiology, including the uptake and processing of nutrients. Both metabolic and circadian regulatory systems are built upon a complex feedback network connecting centres of the central nervous system and different peripheral tissues. Emerging evidence suggests that circadian clock function is closely linked to metabolic homeostasis and that rhythm disruption can contribute to the development of metabolic disease. At the same time, metabolic processes feed back into the circadian clock, affecting clock gene expression and timing of behaviour. In this review, we summarize the experimental evidence for this bimodal interaction, with a focus on the molecular mechanisms mediating this exchange, and outline the implications for clock-based and metabolic diseases.     

细胞自噬与凋亡的交互作用

细胞自唾又称Ⅱ型程序性细胞死亡,参与了多种疾病的发生和发展。自唆与凋亡之间存在着复杂的交互调控——二者能被多种应激刺激共同激活、共享多个调节分子,甚至互相协调转化等。全面深入研究自噬与凋亡之间的交互作用机制,将为肿瘤等疾病的认知及治疗带来突破性进展。