Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides

Moon, Mi‐Young; Kim, Hee‐Jun; Li, Yi; Kim, Jae-Gyu; Jeon, Yee-Jin; Won, Ha-Young; Kim, Jun-Sub; Kwon, Hyeok-Yil; Choi, Ihn-Geun; Ro, Eusun; Joe, Eun‐Hye; Choe, Myeon; Kwon, Hyung‐Joo; Kim, Hyoung‐Chun; Kim, Yong‐Sun; Park, Jae-Bong

doi:10.1016/j.cellsig.2013.05.023

Cited by 24 publications

(19 citation statements)

References 49 publications

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“…In particular, Rac1/2 is involved in activation of p67 PHOX , a component of NOX, leading to superoxide generation (Bokoch & Zhao, ). Here, we emphasize that RhoA has also been reported to regulate superoxide production through indirect activation of NOX (Kim et al, ; Moon et al, ). In addition, Rap1 and RhoA have been reported to have complementary additive functions for superoxide production (Li et al, ).…”

Section: Transcription Factors and Rhoamentioning

confidence: 99%

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway

Kim

Islam

Cho

et al. 2018

Journal Cellular Physiology

106

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RhoA GTPase plays a variety of functions in regulation of cytoskeletal proteins, cellular morphology, and migration along with various proliferation and transcriptional activity in cells. RhoA activity is regulated by guanine nucleotide exchange factors (GEFs), GTPase activating proteins (GAPs), and the guanine nucleotide dissociation factor (GDI). The RhoA-RhoGDI complex exists in the cytosol and the active GTP-bound form of RhoA is located to the membrane. GDI displacement factors (GDFs) including IκB kinase γ (IKKγ) dissociate the RhoA-GDI complex, allowing activation of RhoA through GEFs. In addition, modifications of Tyr42 phosphorylation and Cys16/20 oxidation in RhoA and Tyr156 phosphorylation and oxidation of RhoGDI promote the dissociation of the RhoA-RhoGDI complex. The expression of RhoA is regulated through transcriptional factors such as c-Myc, HIF-1α/2α, Stat 6, and NF-κB along with several reported microRNAs. As the role of RhoA in regulating actin-filament formation and myosin-actin interaction has been well described, in this review we focus on the transcriptional activity of RhoA and also the regulation of RhoA message itself. Of interest, in the cytosol, activated RhoA induces transcriptional changes through filamentous actin (F-actin)-dependent ("actin switch") or-independent means. RhoA regulates the activity of several transcription regulators such as serum response factor (SRF)/MAL, AP-1, NF-κB, YAP/TAZ, β-catenin, and hypoxia inducible factor (HIF)-1α. Interestingly, RhoA also itself is localized to the nucleus by an as-yet-undiscovered mechanism.

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Section: Transcription Factors and Rhoamentioning

confidence: 99%

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway

Kim

Islam

Cho

et al. 2018

Journal Cellular Physiology

106

View full text Add to dashboard Cite

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“…Moreover, activation of the microglial ROCK-axis was associated with cytoskeletal changes and enhanced migration indicating involvement of canonical ROCK-signaling (Bernhart et al, 2010 ). Additionally, superoxide production was increased (Moon et al, 2013 ). In turn, microglia express repellents such as chondroitin sulfate proteoglycans (CSPG) which activate ROCK in neurons, thereby inhibiting axonal regeneration (Monnier et al, 2003 ; Koch et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Chatting with the neighbors: crosstalk between Rho-kinase (ROCK) and other signaling pathways for treatment of neurological disorders

2015

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ROCK inhibition has been largely applied as a strategy to treat neurodegenerative diseases (NDDs) and promising results have been obtained in the recent years. However, the underlying molecular and cellular mechanisms are not fully understood and different models have been proposed for neurodegenerative disorders. Here, we aim to review the current knowledge obtained for NDDs identifying common mechanisms as well as disease-specific models. In addition to the role of ROCK in different cell types such as neurons and microglia, we focus on the molecular signaling-pathways which mediate the beneficial effects of ROCK. Besides canonical ROCK signaling, modulation of neighboring pathways by non-canonical ROCK-crosstalk is a recurrent pattern in many NDD-model systems and has been suggested to mediate beneficial effects of ROCK-inhibition.

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“…The finding that RhoA activation promotes superoxide generation further supports a role for RhoA in the response to and clearance of pathogens . Intriguingly, the generation of superoxide may be sufficient to limit apoptotic cell clearance in professional phagocytes.…”

Section: Additional Branch Points and Regulators Of This Bai1–elmo1–dmentioning

confidence: 73%

Apoptotic cell recognition receptors and scavenger receptors

Penberthy

Ravichandran

2015

Immunological Reviews

168

164

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Summary Phosphatidylserine recognition receptors are a highly diverse set of receptors grouped by their ability to recognize the ‘eat-me’ signal phosphatidylserine on apoptotic cells. Most of the phosphatidylserine recognition receptors dampen inflammation by inducing the production of anti-inflammatory mediators during phagocytosis of apoptotic corpses. However, many phosphatidylserine receptors are also capable of recognizing other ligands, with some receptors being categorized as scavenger receptors. It is now appreciated that these receptors can elicit different downstream events for particular ligands. Therefore, how phosphatidylserine recognition receptors mediate specific signals during recognition of apoptotic cells versus other ligands, and how this might help regulate the inflammatory state of a tissue is an important question that is not fully understood. Here, we revisit the work on signaling downstream of the phosphatidylserine recognition receptor BAI1, and evaluate how these and other signaling modules mediate signaling downstream from other receptors, including Stabilin-2, MerTK and αvβ5. We also propose the concept that phosphatidylserine recognition receptors could be viewed as a subset of scavenger receptors that are capable of eliciting anti-inflammatory responses to apoptotic cells.

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Involvement of small GTPase RhoA in the regulation of superoxide production in BV2 cells in response to fibrillar Aβ peptides

Cited by 24 publications

References 49 publications

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway

Regulation of RhoA GTPase and various transcription factors in the RhoA pathway

Chatting with the neighbors: crosstalk between Rho-kinase (ROCK) and other signaling pathways for treatment of neurological disorders

Apoptotic cell recognition receptors and scavenger receptors

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