scholarly journals Glycans in autophagy, endocytosis and lysosomal functions

Author(s):  
Fulvio Reggiori ◽  
Hans-Joachim Gabius ◽  
Massimo Aureli ◽  
Winfried Römer ◽  
Sandro Sonnino ◽  
...  

AbstractGlycans have been shown to function as versatile molecular signals in cells. This prompted us to look at their roles in endocytosis, endolysosomal system and autophagy. We start by introducing the cell biological aspects of these pathways, the concept of the sugar code, and provide an overview on the role of glycans in the targeting of lysosomal proteins and in lysosomal functions. Moreover, we review evidence on the regulation of endocytosis and autophagy by glycans. Finally, we discuss the emerging concept that cytosolic exposure of luminal glycans, and their detection by endogenous lectins, provides a mechanism for the surveillance of the integrity of the endolysosomal compartments, and serves their eventual repair or disposal.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jong Min Choi ◽  
Seung Eun Baek ◽  
Ji On Kim ◽  
Eun Yeong Jeon ◽  
Eun Jeong Jang ◽  
...  

AbstractMonocyte chemoattractant protein-1 (MCP-1) plays an important role in initiating vascular inflammation; however, its cellular source in the injured vasculatures is unclear. Given the importance of high mobility group box 1 (HMGB1) in tissue injury, we investigated the role of vascular smooth muscle cells (VSMCs) in MCP-1 production in response to HMGB1. In primary cultured rat aortic VSMCs stimulated with HMGB1, the expression of MCP-1 and 5-lipoxygenase (LO) was increased. The increased MCP-1 expression in HMGB1 (30 ng/ml)-stimulated cells was significantly attenuated in 5-LO-deficient cells as well as in cells treated with zileuton, a 5-LO inhibitor. Likewise, MCP-1 expression and production were also increased in cells stimulated with exogenous leukotriene B4 (LTB4), but not exogenous LTC4. LTB4-induced MCP-1 expression was attenuated in cells treated with U75302, a LTB4 receptor 1 (BLTR1) inhibitor as well as in BLTR1-deficient cells, but not in 5-LO-deficient cells. Moreover, HMGB1-induced MCP-1 expression was attenuated in BLTR1-deficient cells or by treatment with a BLTR1 inhibitor, but not other leukotriene receptor inhibitors. In contrast to MCP-1 expression in response to LTB4, the increased MCP-1 production in HMGB1-stimulated VSMC was markedly attenuated in 5-LO-deficient cells, indicating a pivotal role of LTB4-BLTR1 signaling in MCP-1 expression in VSMCs. Taken together, 5-LO-derived LTB4 plays a key role in MCP-1 expression in HMGB1-exposed VSMCs via BLTR1 signaling, suggesting the LTB4-BLTR1 signaling axis as a potential therapeutic target for vascular inflammation in the injured vasculatures.


Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Stephanie Maia Acuña ◽  
Lucile Maria Floeter-Winter ◽  
Sandra Marcia Muxel

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.


2020 ◽  
Vol 11 (1) ◽  
pp. 391-401
Author(s):  
Jiang Cheng ◽  
Guowei Wang ◽  
Na Zhang ◽  
Fang Li ◽  
Lina Shi ◽  
...  

AbstractBackground:Alzheimer’s disease (AD) is an ultimately fatal, degenerative brain disease in the elderly people. In the current work, we assessed the defensive capability of isovitexin (IVX) through an intracerebroventricular injection of streptozotocin (STZ)-induced AD mouse model.Methods:Mice were separated into four cohorts: sham-operated control mice; STZ-intoxicated Alzheimer’s mice; IVX cohort, IVX + STZ; and Ant-107 cohort, antagomiR-107 + IVX/STZ as in the IVX cohort.Results:The outcomes indicated that IVX administration ameliorated spatial memory loss and blunted a cascade of neuro-noxious episodes – including increased amyloid-beta (Aβ) and degraded myelin basic protein burden, neuroinflammation (represented by elevated caspase-1, TNF-α and IL-6 levels) and autophagic dysfunction (represented by altered LC3-II, Atg7 and beclin-1 expressions) – via the inhibition of PI3K/Akt/mTOR signalling axis. We considered the question of whether the epigenetic role of microRNA-107 (miR-107) has any impact on these events, by using antagomiR-107.Conclusion:This probing underscored that miR-107 could be a pivotal regulatory button in the activation of molecular signals linked with the beneficial autophagic process and anti-inflammatory activities in relation to IVX treatment. Hence, this report exemplifies that IVX could guard against Aβ toxicity and serve as an effectual treatment for patients afflicted with AD.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alessia Oppezzo ◽  
Filippo Rosselli

AbstractHaematopoiesis, the process by which a restrained population of stem cells terminally differentiates into specific types of blood cells, depends on the tightly regulated temporospatial activity of several transcription factors (TFs). The deregulation of their activity or expression is a main cause of pathological haematopoiesis, leading to bone marrow failure (BMF), anaemia and leukaemia. TFs can be induced and/or activated by different stimuli, to which they respond by regulating the expression of genes and gene networks. Most TFs are highly pleiotropic; i.e., they are capable of influencing two or more apparently unrelated phenotypic traits, and the action of a single TF in a specific setting often depends on its interaction with other TFs and signalling pathway components. The microphthalmia-associated TF (MiTF) is a prototype TF in multiple situations. MiTF has been described extensively as a key regulator of melanocyte and melanoma development because it acts mainly as an oncogene. Mitf-mutated mice show a plethora of pleiotropic phenotypes, such as microphthalmia, deafness, abnormal pigmentation, retinal degeneration, reduced mast cell numbers and osteopetrosis, revealing a greater requirement for MiTF activity in cells and tissue. A growing amount of evidence has led to the delineation of key roles for MiTF in haematopoiesis and/or in cells of haematopoietic origin, including haematopoietic stem cells, mast cells, NK cells, basophiles, B cells and osteoclasts. This review summarizes several roles of MiTF in cells of the haematopoietic system and how MiTFs can impact BM development.


2021 ◽  
Author(s):  
Kanae Tsubotani ◽  
Sayuri Maeyama ◽  
Shigeru Murakami ◽  
Stephen W Schaffer ◽  
Takashi Ito

AbstractTaurine is a compatible osmolyte that infers stability to proteins. Recent studies have revealed that liquid-liquid phase separation (LLPS) of proteins underlie the formation of membraneless organelles in cells. In the present study, we evaluated the role of taurine on LLPS of hen egg lysozyme. We demonstrated that taurine decreases the turbidity of the polyethylene glycol-induced crowding solution of lysozyme. We also demonstrated that taurine attenuates LLPS-dependent cloudiness of lysozyme solution with 0.5 or 1M NaCl at a critical temperature. Moreover, we observed that taurine inhibits LLPS formation of a heteroprotein mix solution of lysozyme and ovalbumin. These data indicate that taurine can modulate the formation of LLPS of proteins.


Author(s):  
Mohamad Seddigh Mohamadi ◽  
Hasan Babaee ◽  
Mohamad Khaledian

The present paper aims to explain crime by investigating various theoretical approaches and to show that from the classic era to the recent postmodern theories, a slow but steady cycle of discourse concerning crime has been occurring. In the classic times, the criminal is assumed to be a sane person with sound will who commits crime with an individualistic choice and due to incorrect decisions; In the positivism approach, the theorists' concern is directed at recognizing criminals and clarifying more fundamental biological aspects and psychological performance and they seek to explain the phenomenon of crime by dividing the people of the society into normal and abnormal people; In the modern theories the social factors causing the appearance of crime are at the focal point while critical theories greatly emphasize on the role of the society in the criminal phenomenon and its definition, finally postmodern theories consider crime totally as constructed by mindset, language and power and question its existential reality.


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