Hsp27 Upregulation and Phosphorylation Is Required for Injured Sensory and Motor Neuron Survival

Benn, Susanna C.; Perrelet, Daniel; Kato, Ann C.; Scholz, Joachim; Décosterd, Isabelle; Mannion, Richard; Bakowska, Joanna C.; Woolf, Clifford J.

doi:10.1016/s0896-6273(02)00941-8

Cited by 226 publications

(198 citation statements)

References 58 publications

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“…For example, Benn et al[25] showed that the neuroprotective action of HSP27 is downstream of cytochrome c release from mitochondria and upstream of caspase-3 activation. On the other hand, Figueroa et al[38] demonstrated that in cortical neurons nitric oxide toxicity is mediated by mitochondrial dysfunction.…”

Section: Discussionmentioning

confidence: 99%

“…Among these proteins, special attention has been paid to a 27 kDa heat shock protein (HSP27) that is constitutively expressed in some populations of neurons. HSP27 plays an important role in cellular defense mechanisms[242526]. A previous study showed that, 1 week after avulsion of the spinal nerve root, small motor neurons (< 500 µm 2 ) negative for HSP27 immunoreactivity died and only large (> 500 µm 2 ) HSP27-positive motor neurons survived in the spinal cord ventral horn[3].…”

Section: Introductionmentioning

confidence: 99%

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Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis

Ruolin¹,

Zhang²,

Tao³

et al. 2014

Neural Regen Res

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In a previous study, heat shock protein 27 was persistently upregulated in ventral motor neurons following nerve root avulsion or crush. Here, we examined whether the upregulation of heat shock protein 27 would increase the survival rate of motor neurons. Rats were divided into two groups: an avulsion-only group (avulsion of the L4 lumbar nerve root only) and a crush-avulsion group (the L4 lumbar nerve root was crushed 1 week prior to the avulsion). Immunofluorescent staining revealed that the survival rate of motor neurons was significantly greater in the crush-avulsion group than in the avulsion-only group, and this difference remained for at least 5 weeks after avulsion. The higher neuronal survival rate may be explained by the upregulation of heat shock protein 27 expression in motor neurons in the crush-avulsion group. Furthermore, preconditioning crush greatly attenuated the expression of nitric oxide synthase in the motor neurons. Our findings indicate that the neuroprotective action of preconditioning crush is mediated through the upregulation of heat shock protein 27 expression and the attenuation of neuronal nitric oxide synthase upregulation following avulsion.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis

Ruolin¹,

Zhang²,

Tao³

et al. 2014

Neural Regen Res

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“…Several studies indicate a role of HSP27 upregulation in motor neuronal protection and survival (Lewis et al, 1999;Benn et al, 2002;Sharp et al, 2006). The neuroprotective effects of HSP27 may be related to its involvement in neurite extension and branching (Williams et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

“…The heat shock 27kDa protein 1 (HSP27: gene symbol HSPB1; MIM# 602195), is a member of the small heat shock protein family and is constitutively expressed in motor neurons (Plumier et al, 1997). Motor neurons upregulate the expression of HSP27 after peripheral nerve transection and this induction is crucial for their survival (Costigan et al, 1998;Benn et al, 2002;Kalmar et al, 2002). There is also increasing evidence for the neuroprotective capacities of HSP27 overexpression; e.g.…”

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confidence: 99%

Genetic variant in theHSPB1 promoter region impairs the HSP27 stress response

et al. 2007

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The 27kDa heat shock protein 1 (HSP27) is a member of the ubiquitously expressed small heat shock protein family and has pleiotropic cytoprotective functions. Since HSP27 may act as a motor neuron survival factor, we analyzed the genetic contribution of the human HSPB1 gene (HSPB1) to the etiology of amyotrophic lateral sclerosis (ALS). In a cohort of sporadic ALS patients, we identified three rare genetic variations and one of which (c.-217T>C) targeted a conserved nucleotide of the Heat Shock Element (HSE) in the HSPB1 promoter. Since binding of Heat Shock Factor 1 (HSF1) to this HSE is essential for stressinduced transcription of HSPB1, we examined the effect of the c.-217C allele on transcriptional activity and HSF binding. The basal promoter activity of the HSPB1 c.-217C mutant allele decreased to 50% as compared to the wild-type promoter in neuronal and nonneuronal cells. Following heat shock, the HSE variant attenuated significantly the stressrelated increase in transcription. Electrophoretic mobility shift assays demonstrated a dramatically reduced HSF-binding to the c.-217C mutant allele as compared to the c.-217T wild-type allele. In conclusion, our study underscores the importance of the c.-217T nucleotide for HSF binding and heat inducibility of HSPB1. Therefore, our study suggests that the functional HSPB1 variant may represent a genetic modifier in the pathogenesis of motor neuron disease; however, it is necessary to confirm this HSPB1 variant in additional ALS patients. are likely multifactorial processes, including oxidative damage, aggregation, excitotoxicity, inflammation and neurofilament disorganization (Bruijn et al., 2004;Pasinelli and Brown, 2006). Some of these pathogenic processes are known to act as stress stimuli and induce a cellular heat shock response through stress-induced transcription of heat shock proteins (HSPs). Therefore an upregulation of HSPs is seen in several neuronal diseases including ALS (Vleminckx et al., 2002;Bidmon et al., 2004). These HSPs function as molecular chaperones in assisting the correct folding of denatured proteins and by inhibiting cell death pathways. The heat shock 27kDa protein 1 (HSP27: gene symbol HSPB1; MIM# 602195), is a member of the small heat shock protein family and is constitutively expressed in motor neurons (Plumier et al., 1997). Motor neurons upregulate the expression of HSP27 after peripheral nerve transection and this induction is crucial for their survival (Costigan et al., 1998;Benn et al., 2002;Kalmar et al., 2002). There is also increasing evidence for the neuroprotective capacities of HSP27 overexpression; e.g. simultaneous exogenous delivery of HSP27 and HSP70 (gene symbol HSPA1A) protects against copper-zinc superoxide dismutase 1 (SOD1)-mutant induced cell death in mammalian neuronal cells (Bruening et al., 1999;Wagstaff et al., 1999;Wyttenbach et al., 2002;Patel et al., 2005;Batulan et al., 2006), although overexpression of HSP27 alone is insufficient to obtain protection against the toxicity of mutant SOD1 . Furthermore, incr...

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“…3,6,10 Other cellular factors such as heat shock protein (HSP) 27 may be involved in regulating survival and death of neurons. 33 Thus, whether a neuron lives or dies during the period of developmental PCD may be regulated by both extrinsic (e.g., neurotrophic factors) and intrinsic (e.g. Bcl-2 members, HSP27, etc) signals.…”

Section: Discussionmentioning

confidence: 99%

Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

et al. 2005

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Bax is a proapoptotic protein that is required for programmed cell death (PCD) of many neuronal populations. Here we show that, during an early period of retinal PCD and in naturally occurring sensory and motor neuron (MN) death in the spinal cord, Bax delivery results in enhanced death of these neural populations. In contrast, Bax overexpression fails to enhance an early phase of MN death that occurs in the cervical spinal cord, although overexpressed Bax appears to be activated in dying MNs. Bax overexpression does not also affect the survival of immature neurons prior to the PCD period. Taken together, these data provide the first in vivo evidence suggesting that Bax appears to act selectively as an executioner only in neurons undergoing PCD. Furthermore, although Bax appears to mediate the execution pathway for PCD, the effect of Bax overexpression on susceptibility to death differs between different neuronal populations.

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Hsp27 Upregulation and Phosphorylation Is Required for Injured Sensory and Motor Neuron Survival

Cited by 226 publications

References 58 publications

Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis

Effect of dexamethasone on intelligence and hearing in preterm infants: a meta-analysis

Genetic variant in theHSPB1 promoter region impairs the HSP27 stress response

Distinct susceptibility of developing neurons to death following Bax overexpression in the chicken embryo

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