Role of hsp105 in Protection against Stress-Induced Apoptosis in Neuronal PC12 Cells

Hatayama, Takumi; Yamagishi, Nobuyuki; Minobe, Etsuko; Sakai, Kayo

doi:10.1006/bbrc.2001.5802

Cited by 61 publications

(69 citation statements)

References 30 publications

(28 reference statements)

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“…The gene XRCC3 (Gene ID 7517) encodes an RecA/Rad51-related protein, and it promotes homology-directed DNA damage repair in mammalian cells (34) and correct chromosome segregation (35). HSP105 (Gene ID 15505) is a major heat shock protein, and it can protect against stress-induced apoptosis (36) and reduce the aggregation of denatured proteins and cytotoxicity (37). LMTK1 (Gene ID 9625) regulates neuronal cell differentiation (38,39) and is also selected in the AS.…”

Section: Resultsmentioning

confidence: 99%

Sympatric speciation of spiny mice, Acomys , unfolded transcriptomically at Evolution Canyon, Israel

Wang

Cai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Spiny mice, Acomys cahirinus, colonized Israel 30,000 y ago from dry tropical Africa and inhabited rocky habitats across Israel. Earlier, we had shown by mtDNA that A. cahirinus incipiently sympatrically speciates at Evolution Canyon I (EC I) in Mount Carmel, Israel because of microclimatic interslope divergence. The EC I microsite consists of a dry and hot savannoid "African" slope (AS) and an abutting humid and cool-forested "European" slope (ES). Here, we substantiate incipient SS in A. cahirinus at EC I based on the entire transcriptome, showing that multiple slope-specific adaptive complexes across the transcriptome result in two divergent clusters. Tajima's D distribution of the abutting Acomys interslope populations shows that the ES population is under stronger positive selection, whereas the AS population is under balancing selection, harboring higher genetic polymorphisms. Considerable sites of the two populations were differentiated with a coefficient of F ST = 0.25-0.75. Remarkably, 24 and 37 putatively adaptively selected genes were detected in the AS and ES populations, respectively. The AS genes involved DNA repair, growth arrest, neural cell differentiation, and heat-shock proteins adapting to the local AS stresses of high solar radiation, drought, and high temperature. In contrast, the ES genes involved high ATP associated with energetics stress. The sharp ecological interslope divergence led to strong slope-specific selection overruling the interslope gene flow. Earlier tests suggested slope-specific mate choice. Habitat interslope-adaptive selection across the transcriptome and mate choice substantiate sympatric speciation (SS), suggesting its prevalence at EC I and commonality in nature.adaptive ecological speciation | microclimate | natural selection | RNA-seq

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Section: Resultsmentioning

confidence: 99%

Sympatric speciation of spiny mice, Acomys , unfolded transcriptomically at Evolution Canyon, Israel

Wang

Cai

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Hsp105␣ is a stress protein expressed at an especially high level in mammalian brain (43) and has an antiapoptotic effect in neuronal cells (44). Hsp105␣ prevents the aggregation of denatured proteins caused by heat shock in vitro but has not been shown to have chaperone activity (45).…”

Section: Discussionmentioning

confidence: 99%

“…Although the relationship between the aggregation and the induction of apoptosis remains unknown, the suppression of cellular toxicity by molecular chaperones may be caused by the ability to inhibit apoptosis. Hsp105␣ suppresses heat shockinduced apoptosis in neuronal cells by preventing the activation of c-Jun N-terminal kinase (44). Because c-Jun N-terminal kinase is activated by the expanded polyglutamine tract (58), Hsp105␣ may also suppress the cellular toxicity by its ability to inhibit apoptosis.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, the increased amounts of Hsp105␣ in cells seemed necessary for the interaction with and binding to the tAR containing an expanded polyglutamine tract. (45) and suppresses apoptotic cell death induced by various forms of stress in neuronal PC12 cells (44). Because the overexpressed Hsp105␣ colocalized to intracellular aggregates of tAR97 (Fig.…”

Section: Colocalization Of Hsp105␣ and Hsp70 With Aggregates Of Truncmentioning

confidence: 91%

“…Recently, Hsp105␣ was demonstrated to have antiapoptotic properties for neuronal survival (44). Furthermore, Hsp105␣ prevents the aggregation of thermal denatured protein in vitro (45).…”

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confidence: 99%

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Hsp105α Suppresses the Aggregation of Truncated Androgen Receptor with Expanded CAG Repeats and Cell Toxicity

Ishihara

Yamagishi

Saito

et al. 2003

Journal of Biological Chemistry

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Spinal and bulbar muscular atrophy (SBMA) is a neurodegenerative disorder caused by the expansion of a polyglutamine tract in the androgen receptor (AR). The N-terminal fragment of AR containing the expanded polyglutamine tract aggregates in cytoplasm and/or in nucleus and induces cell death. Some chaperones such as Hsp40 and Hsp70 have been identified as important regulators of polyglutamine aggregation and/or cell death in neuronal cells. Recently, Hsp105␣, expressed at especially high levels in mammalian brain, has been shown to suppress apoptosis in neuronal cells and prevent the aggregation of protein caused by heat shock in vitro. However, its role in polyglutamine-mediated cell death and toxicity has not been studied. In the present study, we examined the effects of Hsp105␣ on the aggregation and cell toxicity caused by expansion of the polyglutamine tract using a cellular model of SBMA. The transient expression of truncated ARs (tARs) containing an expanded polyglutamine tract caused aggregates to form in COS-7 and SK-N-SH cells and concomitantly apoptosis in the cells with the nuclear aggregates. When Hsp105␣ was overexpressed with tAR97 in the cells, Hsp105␣ was colocalized to aggregates of tAR97, and the aggregation and cell toxicity caused by expansion of the polyglutamine tract were markedly reduced. Both ␤-sheet and ␣-helix domains, but not the ATPase domain, of Hsp105␣ were necessary to suppress the formation of aggregates in vivo and in vitro. Furthermore, Hsp105␣ was found to localize in nuclear inclusions formed by ARs containing an expanded polyglutamine tract in tissues of patients and transgenic mice with SBMA. These findings suggest that overexpression of Hsp105␣ suppresses cell death caused by expansion of the polyglutamine tract without chaperone activity, and the enhanced expression of the essential domains of Hsp105␣ in brain may provide an effective therapeutic approach for CAG repeat diseases.

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Gene expression differences over a critical period of afferent-dependent neuron survival in the mouse auditory brainstem

et al. 2005

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Deprivation of auditory nerve input in young mice results in dramatic neuron death in the anteroventral cochlear nucleus (CN), while the same manipulation performed in older mice does not result in significant neuronal loss. The molecular basis underlying this critical period of susceptibility to loss of afferent input remains largely unknown. One possibility is that developmental differences in baseline mRNA expression of specific genes could predispose CN neurons to either death or survival after deafferentation. We used two microarray platforms to identify differentially expressed genes in the CN during and after this critical period. Results across platforms were also compared to each other. Three ages were examined; during the critical period (postnatal day (P)7), at the closing of the critical period (P14), and 1 week after the critical period (P21). Of all the genes surveyed (22,690 or 15,247), 1,082 were identified as significantly changed in expression during the critical period relative to after. Real-time reverse transcription polymerase chain reaction and immunohistochemistry confirmed and extended the microarray results for a subset of these genes. Further analysis of genes related to apoptotic pathways showed 6 out of 7 differentially expressed known pro-apoptotic genes had higher expression during the critical period. In contrast, 9 out of 11 differentially expressed known pro-survival genes increased after the critical period when CN neurons survive deprivation. This finding supports the concept that multiple neuroprotective mechanisms increase and pro-apoptotic factors decrease over development to protect mature neurons from stressful insults, making them less dependent on afferent input for survival.

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Role of hsp105 in Protection against Stress-Induced Apoptosis in Neuronal PC12 Cells

Cited by 61 publications

References 30 publications

Sympatric speciation of spiny mice, Acomys , unfolded transcriptomically at Evolution Canyon, Israel

Sympatric speciation of spiny mice, Acomys , unfolded transcriptomically at Evolution Canyon, Israel

Hsp105α Suppresses the Aggregation of Truncated Androgen Receptor with Expanded CAG Repeats and Cell Toxicity

Gene expression differences over a critical period of afferent-dependent neuron survival in the mouse auditory brainstem

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