Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction

Rajdev, Sunita; Hara, Kazushi; Kokubo, Yasuaki; Mestril, Ruben; Dillmann, Wolfgang H.; Weinstein, Philip; Sharp, Frank R.

doi:10.1002/1531-8249(200006)47:6<782::aid-ana11>3.0.co;2-3

Cited by 260 publications

(185 citation statements)

References 45 publications

Supporting

Mentioning

169

Contrasting

Unclassified

Order By: Relevance

“…PDI A3, Hsc70 and Hsp60 are heat shock proteins involved in cellular repair, recovery and survival [17][18][19][20][21] whereas CRMP-2 performs functions related to neurite outgrowth [17,[22][23][24][25]. The RSA found in the brain extracts could result from contamination of the samples by vascular contents which are unavoidably included in the samples.…”

Section: Discussionmentioning

confidence: 99%

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

Anagli

Abounit

Stemmer

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

The effects of selective inhibition of cathepsins B and L on postischemic protein alterations in the brain were investigated in a rat model of middle cerebral artery occlusion (MCAO). Cathepsin B activity increased predominantly in the subcortical region of the ischemic hemisphere where the levels of collapsing mediator response protein 2, heat shock cognate 70 kDa protein, 60 kDa heat shock protein, protein disulfide isomerase A3 and albumin, were found to be significantly elevated. Postischemic treatment with Cbz-Phe-Ser(OBzl)-CHN 2 , cysteine protease inhibitor 1 (CP-1), reduced infarct volume, neurological deficits and cathepsin B activity as well as the amount of heat shock proteins and albumin found in the brain. Our data strongly suggests that the decrease in heat shock protein levels and the significant reduction of serum albumin leakage into the brain following acute treatment with CP-1 is indicative of less secondary ischemic damage, which ultimately, is related to less cerebral tissue loss and improved neurological recovery of the animals.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

Anagli

Abounit

Stemmer

et al. 2008

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…77 The crucial role of HSP70 is confirmed by studies that show that HSP70 overexpression alone attenuates ischemic damage and seizures. [109][110][111] Interestingly, not only the histones at their expected location in the nucleus of the cell are involved in poststroke apoptotic processes. Dead cells release chromatin and as a result, the overall levels of circulating nucleosomes and DNA fragments are increased after an ischemic injury.…”

Section: Excitotoxicitymentioning

confidence: 99%

Epigenetic Mechanisms in Cerebral Ischemia

Schweizer

Meisel

Märschenz

2013

J Cereb Blood Flow Metab

View full text Add to dashboard Cite

Treatment efficacy for ischemic stroke represents a major challenge. Despite fundamental advances in the understanding of stroke etiology, therapeutic options to improve functional recovery remain limited. However, growing knowledge in the field of epigenetics has dramatically changed our understanding of gene regulation in the last few decades. According to the knowledge gained from animal models, the manipulation of epigenetic players emerges as a highly promising possibility to target diverse neurologic pathologies, including ischemia. By altering transcriptional regulation, epigenetic modifiers can exert influence on all known pathways involved in the complex course of ischemic disease development. Beneficial transcriptional effects range from attenuation of cell death, suppression of inflammatory processes, and enhanced blood flow, to the stimulation of repair mechanisms and increased plasticity. Most striking are the results obtained from pharmacological inhibition of histone deacetylation in animal models of stroke. Multiple studies suggest high remedial qualities even upon late administration of histone deacetylase inhibitors (HDACi). In this review, the role of epigenetic mechanisms, including histone modifications as well as DNA methylation, is discussed in the context of known ischemic pathways of damage, protection, and regeneration.

show abstract

“…Dramatic upregulation of HSPs in response to stress is known as 'the heat-shock response'. The HSPs of the 70 kDa family, HSP72 (cytosol), GRP75 (mitochondria), and GRP78/BIP (endoplasmic reticulum), are evolutionarily conserved proteins that promote neuronal survival/protection in animal models of stroke (Rajdev et al, 2000;Hoehn et al, 2001;Kudo et al, 2008;Oida et al, 2008). A recent study identified miR-181 as a possible regulator of several HSP70 family members and validated HSP GRP78/BIP to be a target of miR-181 in response to ischemic brain injury.…”

Section: The Role Of Micrornas In Strokementioning

confidence: 99%

Epigenetic Mechanisms in Stroke and Epilepsy

Hwang

Aromolaran

Zukin

2012

Neuropsychopharmacol

View full text Add to dashboard Cite

Epigenetic remodeling and modifications of chromatin structure by DNA methylation and histone modifications represent central mechanisms for the regulation of neuronal gene expression during brain development, higher-order processing, and memory formation. Emerging evidence implicates epigenetic modifications not only in normal brain function, but also in neuropsychiatric disorders. This review focuses on recent findings that disruption of chromatin modifications have a major role in the neurodegeneration associated with ischemic stroke and epilepsy. Although these disorders differ in their underlying causes and pathophysiology, they share a common feature, in that each disorder activates the gene silencing transcription factor REST (repressor element 1 silencing transcription factor), which orchestrates epigenetic remodeling of a subset of 'transcriptionally responsive targets' implicated in neuronal death. Although ischemic insults activate REST in selectively vulnerable neurons in the hippocampal CA1, seizures activate REST in CA3 neurons destined to die. Profiling the array of genes that are epigenetically dysregulated in response to neuronal insults is likely to advance our understanding of the mechanisms underlying the pathophysiology of these disorders and may lead to the identification of novel therapeutic strategies for the amelioration of these serious human conditions.

show abstract

Mice overexpressing rat heat shock protein 70 are protected against cerebral infarction

Cited by 260 publications

References 45 publications

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

Effects of cathepsins B and L inhibition on postischemic protein alterations in the brain

Epigenetic Mechanisms in Cerebral Ischemia

Epigenetic Mechanisms in Stroke and Epilepsy

Contact Info

Product

Resources

About