Abnormal mitosis in reactive astrocytes

The formation of abnormal mitosis associated with cancer has been intriguing for many decades. While microtubules had been the focus of previous studies, recent research has focused on centrosomes, microtubule organizing centers which organize the mitotic apparatus during cell division. During normal mitosis centrosomes form two poles but in cancer, centrosomes can form three, four, or more poles, and organize tripolar, quadripolar, and multipolar mitoses, respectively. This has severe consequences for genomic stability because chromosomes are separated unequally to three, four, or more poles. This can result in aneuploidy and gene amplifications with multiple defects in cellular regulation. It can result in malignancy that is accompanied by cell cycle imbalances and abnormal cell proliferation. While radiation and chemical agents are known to damage DNA and can lead to cell cycle abnormalities, the damage of centrosome structure leading to abnormal mitosis deserves also consideration.

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Bi-directional network remodeling by reactive astrocytes

IBRO Reports ◽

10.1016/j.ibror.2019.07.034 ◽

2019 ◽

Vol 6 ◽

pp. S15

Author(s):

Schuichi Koizumi

Keyword(s):

Reactive Astrocytes

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Induction of apoptotic cell death preferentially in reactive astrocytes by concanavalin A

Journal of Bioscience and Bioengineering ◽

10.1016/j.jbiosc.2009.03.023 ◽

2009 ◽

Vol 108 (3) ◽

pp. 248-251 ◽

Cited By ~ 3

Author(s):

Hideki Yoshida ◽

Kaoru Nagai

Keyword(s):

Cell Death ◽

Concanavalin A ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Reactive Astrocytes

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The Key Regulator of Necroptosis, RIP1 Kinase, Contributes to the Formation of Astrogliosis and Glial Scar in Ischemic Stroke

Translational Stroke Research ◽

10.1007/s12975-021-00888-3 ◽

2021 ◽

Author(s):

Yong-Ming Zhu ◽

Liang Lin ◽

Chao Wei ◽

Yi Guo ◽

Yuan Qin ◽

...

Keyword(s):

Ischemic Stroke ◽

Glucose Deprivation ◽

Artery Occlusion ◽

Glial Scar ◽

Scar Formation ◽

Reactive Astrocytes ◽

Interacting Protein ◽

Protein Levels ◽

Endothelial Growth Factor ◽

Cerebral Artery Occlusion

AbstractNecroptosis initiation relies on the receptor-interacting protein 1 kinase (RIP1K). We recently reported that genetic and pharmacological inhibition of RIP1K produces protection against ischemic stroke-induced astrocytic injury. However, the role of RIP1K in ischemic stroke-induced formation of astrogliosis and glial scar remains unknown. Here, in a transient middle cerebral artery occlusion (tMCAO) rat model and an oxygen and glucose deprivation and reoxygenation (OGD/Re)-induced astrocytic injury model, we show that RIP1K was significantly elevated in the reactive astrocytes. Knockdown of RIP1K or delayed administration of RIP1K inhibitor Nec-1 down-regulated the glial scar markers, improved ischemic stroke-induced necrotic morphology and neurologic deficits, and reduced the volume of brain atrophy. Moreover, knockdown of RIP1K attenuated astrocytic cell death and proliferation and promoted neuronal axonal generation in a neuron and astrocyte co-culture system. Both vascular endothelial growth factor D (VEGF-D) and its receptor VEGFR-3 were elevated in the reactive astrocytes; simultaneously, VEGF-D was increased in the medium of astrocytes exposed to OGD/Re. Knockdown of RIP1K down-regulated VEGF-D gene and protein levels in the reactive astrocytes. Treatment with 400 ng/ml recombinant VEGF-D induced the formation of glial scar; conversely, the inhibitor of VEGFR-3 suppressed OGD/Re-induced glial scar formation. RIP3K and MLKL may be involved in glial scar formation. Taken together, these results suggest that RIP1K participates in the formation of astrogliosis and glial scar via impairment of normal astrocyte responses and enhancing the astrocytic VEGF-D/VEGFR-3 signaling pathways. Inhibition of RIP1K promotes the brain functional recovery partially via suppressing the formation of astrogliosis and glial scar. Graphical Abstract

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Endothelin ETB Receptor-Mediated Astrocytic Activation: Pathological Roles in Brain Disorders

International Journal of Molecular Sciences ◽

10.3390/ijms22094333 ◽

2021 ◽

Vol 22 (9) ◽

pp. 4333

Author(s):

Yutaka Koyama

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Neurotrophic Factors ◽

Drug Target ◽

Therapeutic Strategy ◽

Reactive Astrocytes ◽

Brain Disorders ◽

Etb Receptor ◽

Target Molecules ◽

Endothelin B

In brain disorders, reactive astrocytes, which are characterized by hypertrophy of the cell body and proliferative properties, are commonly observed. As reactive astrocytes are involved in the pathogenesis of several brain disorders, the control of astrocytic function has been proposed as a therapeutic strategy, and target molecules to effectively control astrocytic functions have been investigated. The production of brain endothelin-1 (ET-1), which increases in brain disorders, is involved in the pathophysiological response of the nervous system. Endothelin B (ETB) receptors are highly expressed in reactive astrocytes and are upregulated by brain injury. Activation of astrocyte ETB receptors promotes the induction of reactive astrocytes. In addition, the production of various astrocyte-derived factors, including neurotrophic factors and vascular permeability regulators, is regulated by ETB receptors. In animal models of Alzheimer’s disease, brain ischemia, neuropathic pain, and traumatic brain injury, ETB-receptor-mediated regulation of astrocytic activation has been reported to improve brain disorders. Therefore, the astrocytic ETB receptor is expected to be a promising drug target to improve several brain disorders. This article reviews the roles of ETB receptors in astrocytic activation and discusses its possible applications in the treatment of brain disorders.

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