Activation of autophagy during glutamate-induced HT22 cell death

Kim, Han‐Soo; Choi, Jin-Sun; Ryu, Joohyun; Park, Sung Goo; Cho, Sayeon; Park, Byoung Chul; Lee, Do Hee

doi:10.1016/j.bbrc.2009.08.007

Cited by 44 publications

(36 citation statements)

References 32 publications

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“…HSP60 was present in connective tissue, associated with infiltrates, with muscle fibers surrounded or invaded by infiltrates, mostly in PM and sIBM, and with capillaries and large blood vessels, mainly in DM and JDM. Like HMGB1, HSP60 has been suggested to be involved in the induction of autophagy [27]. Our finding that HSP60 and LC3 co-localized in all 16 IIM muscles examined, is consisted with HSP60 involvement in autophagy.…”

Section: Discussionsupporting

confidence: 53%

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Autophagy, Inflammation and Innate Immunity in Inflammatory Myopathies

et al. 2014

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Autophagy has a large range of physiological functions and its dysregulation contributes to several human disorders, including autoinflammatory/autoimmune diseases such as inflammatory myopathies (IIMs). In order to better understand the pathogenetic mechanisms of these muscular disorders, we sought to define the role of autophagic processes and their relation with the innate immune system in the three main subtypes of IIM, specifically sporadic inclusion body myositis (sIBM), polymyositis (PM), dermatomyositis (DM) and juvenile dermatomyositis (JDM). We found that although the mRNA transcript levels of the autophagy-related genes BECN1, ATG5 and FBXO32 were similar in IIM and controls, autophagy activation in all IIM subgroups was suggested by immunoblotting results and confirmed by immunofluorescence. TLR4 and TLR3, two potent inducers of autophagy, were highly increased in IIM, with TLR4 transcripts significantly more expressed in PM and DM than in JDM, sIBM and controls, and TLR3 transcripts highly up-regulated in all IIM subgroups compared to controls. Co-localization between autophagic marker, LC3, and TLR4 and TLR3 was observed not only in sIBM but also in PM, DM and JDM muscle tissues. Furthermore, a highly association with the autophagic processes was observed in all IIM subgroups also for some TLR4 ligands, endogenous and bacterial HSP60, other than the high-mobility group box 1 (HMGB1). These findings indicate that autophagic processes are active not only in sIBM but also in PM, DM and JDM, probably in response to an exogenous or endogenous ‘danger signal’. However, autophagic activation and regulation, and also interaction with the innate immune system, differ in each type of IIM. Better understanding of these differences may lead to new therapies for the different IIM types.

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Section: Discussionsupporting

confidence: 53%

“…Since HSP60 is involved in macroautophagy [27], [28], we investigated whether endogenous HSP60 co-localized with LC3 in IIM. We investigated 4 PM, 4 sIBM, 4 DM, 4 JDM and 4 control muscles.…”

Section: Resultsmentioning

confidence: 99%

Autophagy, Inflammation and Innate Immunity in Inflammatory Myopathies

et al. 2014

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“…28 Moreover, autophagic cell death was induced in glutamate-mediated neurotoxicity and in experimental spinal cord injury (SCI). 29, 30, 31 Here, we have shown for the first time that TBI-induced cytotoxicity in astrocytes occurs through autophagic and apoptotic cell death in vivo and in vitro . Although apoptosis and autophagy are classed as type I and type II programmed cell death, respectively, numerous studies have addressed the relationship between autophagy and apoptosis.…”

Section: Discussionmentioning

confidence: 78%

Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death

et al. 2014

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Traumatic brain injury (TBI) is often caused by accidents that damage the brain. TBI can induce glutamate excitotoxicity and lead to neuronal and glial cell death. In this study, we investigated the mechanism of cell death during the secondary damage caused by TBI in vivo and in vitro, as well as the protective effect of resveratrol (RV). Here we report that glycogen synthase kinase-3β (GSK-3β) activation and microtubule-associated protein light chain 3 processing were induced in rat brains exposed to TBI. In the in vitro TBI model, apoptotic and autophagic cell death were induced through glutamate-mediated GSK-3β activation in normal CTX TNA2 astrocytes. The GSK-3β inhibitor SB216763 or transfection of GSK-3β small-interfering RNA increases cell survival. By contrast, overexpression of GSK-3β enhanced glutamate excitotoxicity. Administration of RV reduced cell death in CTX TNA2 astrocytes by suppressing reactive oxygen species (ROS)-mediated GSK-3β activation, the mechanism by which RV also exerted protective effects in vivo. Mitochondrial damages, including the opening of mitochondrial permeability transition pore (MPTP) and mitochondrial depolarization, were induced by glutamate through the ROS/GSK-3β pathway. Moreover, cyclosporine A, an MPTP inhibitor, suppressed mitochondrial damage and the percentages of cells undergoing autophagy and apoptosis and thereby increased cell survival. Taken together, our results demonstrated that cell death occurring after TBI is induced through the ROS/GSK-3β/mitochondria signaling pathway and that administration of RV can increase cell survival by suppressing GSK-3β-mediated autophagy and apoptosis. Therefore, the results indicated that resveratrol may serve as a potential therapeutic agent in the treatment of TBI.

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“…Growth factor deprivation in purkinje neurons (Canu et al , 2005) and sympathetic neurons (Xue et al , 1999) leads to accumulation of autophagic vesicles and cell death. Exposure to glutamate, potassium deprivation, and staurosporine can result in cell death through autophagy (Canu et al , 2005; Kim et al , 2009; Maycotte et al , 2010). Methamphatamine leads to neuronal cell death not only through apoptosis, but also through autophagy by inhibiting the disassociation of the Bcl-2/Beclin 1 complex (Nopparat et al , 2010).…”

Section: Mtor and Cellular Demise With Oxidant Stress Apoptosis mentioning

confidence: 99%

Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

Chong¹,

Shang

Wang

et al. 2012

Progress in Neurobiology

105

118

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Neurodegenerative disorders affect a significant portion of the world's population leading to either disability or death for almost 30 million individuals worldwide. One novel therapeutic target that may offer promise for multiple disease entities that involve Alzheimer's disease, Parkinson's disease, epilepsy, trauma, stroke, and tumors of the nervous system is the mammalian target of rapamycin (mTOR). mTOR signaling is dependent upon the mTORC1 and mTORC2 complexes that are composed of mTOR and several regulatory proteins including the tuberous sclerosis complex (TSC1, hamartin/ TSC2, tuberin). Through a number of integrated cell signaling pathways that involve those of mTORC1 and mTORC2 as well as more novel signaling tied to cytokines, Wnt, and forkhead, mTOR can foster stem cellular proliferation, tissue repair and longevity, and synaptic growth by modulating mechanisms that foster both apoptosis and autophagy. Yet, mTOR through its proliferative capacity may sometimes be detrimental to central nervous system recovery and even promote tumorigenesis. Further knowledge of mTOR and the critical pathways governed by this serine/threonine protein kinase can bring new light for neurodegeneration and other related diseases that currently require new and robust treatments.

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Activation of autophagy during glutamate-induced HT22 cell death

Cited by 44 publications

References 32 publications

Autophagy, Inflammation and Innate Immunity in Inflammatory Myopathies

Autophagy, Inflammation and Innate Immunity in Inflammatory Myopathies

Resveratrol protects astrocytes against traumatic brain injury through inhibiting apoptotic and autophagic cell death

Shedding new light on neurodegenerative diseases through the mammalian target of rapamycin

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