Rac1 and Cdc42 Play Important Roles in Arsenic Neurotoxicity in Primary Cultured Rat Cerebellar Astrocytes

An, Yuan; Liu, Tingting; Liu, Xiaona; Zhao, Liyun; Wang, Jing

doi:10.1007/s12011-015-0456-7

Cited by 9 publications

(6 citation statements)

References 49 publications

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“…The high expression of Rac1 can inhibit astrocyte outgrowth [ 59 ]. Meanwhile, Rac1 and Cdc42 can cause astrocyte apoptosis induced by neurotoxicity [ 60 ]. In addition, activation of Rac1 and Cdc42 can change microglia into the M2-like phenotype, which is beneficial in CNS regeneration [ 61 ].…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury

et al. 2019

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Exosomes are nanometer-sized vesicles involved in intercellular communication, and they are released by various cell types. To learn about exosomes produced by Schwann cells (SCs) and to explore their potential function in repairing the central nervous system (CNS), we isolated exosomes from supernatants of SCs by ultracentrifugation, characterized them by electron microscopy and immunoblotting and determined their protein profile using proteomic analysis. The results demonstrated that Schwann cell-derived exosomes (SCDEs) were, on average, 106.5 nm in diameter, round, and had cup-like concavity and expressed exosome markers CD9 and Alix but not tumor susceptibility gene (TSG) 101. We identified a total of 433 proteins, among which 398 proteins overlapped with the ExoCarta database. According to their specific functions, we identified 12 proteins that are closely related to CNS repair and classified them by different potential mechanisms, such as axon regeneration and inflammation inhibition. Gene Oncology analysis indicated that SCDEs are mainly involved in signal transduction and cell communication. Biological pathway analysis showed that pathways are mostly involved in exosome biogenesis, formation, uptake and axon regeneration. Among the pathways, the neurotrophin, PI3K-Akt and cAMP signaling pathways played important roles in CNS repair. Our study isolated SCDEs, unveiled their contents, presented potential neurorestorative proteins and pathways and provided a rich proteomics data resource that will be valuable for future studies of the functions of individual proteins in neurodegenerative diseases. Electronic supplementary material The online version of this article (10.1007/s11010-019-03511-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury

et al. 2019

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“…For example, ZCL278 can restrain the migratory and invasive characteristics of the prostate cancer cell line PC3 in vitro [139]. In addition, it can also prevent the toxicity of sodium arsenite (NaAsO 2 ) on astrocytes and cerebellar granule neurons, encouraging its use to alleviate arsenic poisoning on the nervous system [141,142].…”

Section: Cdc42 and Its Inhibitors In Cancer Therapymentioning

confidence: 99%

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Prieto-Domínguez

Parnell

Teng

2019

Cells

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Small GTPases are a family of low molecular weight GTP-hydrolyzing enzymes that cycle between an inactive state when bound to GDP and an active state when associated to GTP. Small GTPases regulate key cellular processes (e.g., cell differentiation, proliferation, and motility) as well as subcellular events (e.g., vesicle trafficking), making them key participants in a great array of pathophysiological processes. Indeed, the dysfunction and deregulation of certain small GTPases, such as the members of the Ras and Arf subfamilies, have been related with the promotion and progression of cancer. Therefore, the development of inhibitors that target dysfunctional small GTPases could represent a potential therapeutic strategy for cancer treatment. This review covers the basic biochemical mechanisms and the diverse functions of small GTPases in cancer. We also discuss the strategies and challenges of inhibiting the activity of these enzymes and delve into new approaches that offer opportunities to target them in cancer therapy.

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“…The key molecule for directed elongation of astrocytes is the small GTPase Cdc42, which regulates the arrangement of microtubule tissue centers (MTOCs) and Golgi through the mPar6-PKCzeta signaling pathway. Cdc42 polarizes transport of cytoskeletal regulators towards the leading edge to force microtubules to the tip of the protrusion; thereby, elongating the processes of reactive astrocytes (An et al, 2016;Robel et al, 2011). Significant up-regulation of IF in reactive astrogliosis performs the function of maintaining cell polarity and orientation of both motion and nuclear localization.…”

Section: Morphological Changes Proliferation and Migration Of Astrocmentioning

confidence: 99%

Morphological and functional alterations of astrocytes responding to traumatic brain injury

Cheng

Wang

Xiao

et al. 2019

J. Integr. Neurosci.

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Astrocytes, one of the most abundant and heterogeneous types of glial cell in the brain and spinal cord, are responsible for various essential functions in the healthy central nervous system, including maintaining the blood brain barrier integrity, regulating neuron differentiation and supporting, nourishing, protecting, insulating and repairing neurons. They also fulfill a range of other homeostatic maintenance functions. Astrocytes are activated after traumatic brain injury. They then exhibit heterogeneous gene expression and changes in morphology, proliferative capacity and various functions in response either acute or chronic brain injury and associated secondary brain injury. Some biomarkers and imaging tools have been used to monitor astrogliosis after traumatic brain injury. Initially, morphological characteristics and the physiology of astrocytes are reviewed. Subsequently, alterations of astrocytes are described, which includes both the complex mechanisms and roles of reactive astrocytes. The roles of biomarkers and signaling pathways following traumatic brain injury have been summarized as well as the morphological and functional changes in astrocytes. In the latter case, by considering astrocytes as therapeutic targets of traumatic brain injury, the mechanisms of the latest drug treatments are explained. This review highlights the beneficial effects of astrogliosis according to some recent findings, which provides new insights for the treatment of traumatic brain injury.

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Rac1 and Cdc42 Play Important Roles in Arsenic Neurotoxicity in Primary Cultured Rat Cerebellar Astrocytes

Cited by 9 publications

References 49 publications

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury

Proteomics analysis of Schwann cell-derived exosomes: a novel therapeutic strategy for central nervous system injury

Drugging the Small GTPase Pathways in Cancer Treatment: Promises and Challenges

Morphological and functional alterations of astrocytes responding to traumatic brain injury

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