Astragalus injection protects cerebral ischemic injury by inhibiting neuronal apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats

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Abstract

Background

Astragalus is a widely used traditional Chinese medicine and has been proven beneficial for many aspects of human health. It is important to explore the neuroprotective effect and mechanism of astragalus injection in cerebral ischemia reperfusion injury.

Methods

The focal cerebral ischemic model with middle cerebral artery occlusion (MCAO) reperfusion was established by Longa’s method in healthy adult male Wistar rats, and treated by injecting intraperitoneally astragalus injection (3 ml/kg). The neurobehavioral function of rats was evaluated by Longa’s test. The cerebral blood flow (CBF) was measured by laser Doppler flowmetry and the cerebral infarct volume was calculated by tetrazolium chloride (TTC) stain. The shape and structure of neurons in parahippocampal area was observed by HE stain and the neuronal apoptosis was detected by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling (TUNEL) and flow cytometry. The expressions of c-jun N-terminal kinase 3 (JNK3) mRNA and protein were determined by RT-PCR and immunohistochemical assay and Western blotting respectively.

Results

After treatment with astragalus injection, the expressions of JNK3 mRNA and protein reduced significantly, the number of neuronal apoptosis minus, the cerebral infarct volume shrink, the neuronal shape-structure and animal neurobehavioral function improved significantly than those in model rats.

Conclusions

It is suggested that astragalus injection could inhibit neuronal apoptosis, reduce infarct volume and improve neurobehavioral function by down-regulating the expression of JNK3 gene after cerebral ischemia reperfusion injury in rats.

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Most cited references 12

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Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.

Marie A. Bogoyevitch, Bostjan Kobe (2006)

The c-Jun N-terminal kinases (JNKs) are members of a larger group of serine/threonine (Ser/Thr) protein kinases from the mitogen-activated protein kinase family. JNKs were originally identified as stress-activated protein kinases in the livers of cycloheximide-challenged rats. Their subsequent purification, cloning, and naming as JNKs have emphasized their ability to phosphorylate and activate the transcription factor c-Jun. Studies of c-Jun and related transcription factor substrates have provided clues about both the preferred substrate phosphorylation sequences and additional docking domains recognized by JNK. There are now more than 50 proteins shown to be substrates for JNK. These include a range of nuclear substrates, including transcription factors and nuclear hormone receptors, heterogeneous nuclear ribonucleoprotein K, and the Pol I-specific transcription factor TIF-IA, which regulates ribosome synthesis. Many nonnuclear substrates have also been characterized, and these are involved in protein degradation (e.g., the E3 ligase Itch), signal transduction (e.g., adaptor and scaffold proteins and protein kinases), apoptotic cell death (e.g., mitochondrial Bcl2 family members), and cell movement (e.g., paxillin, DCX, microtubule-associated proteins, the stathmin family member SCG10, and the intermediate filament protein keratin 8). The range of JNK actions in the cell is therefore likely to be complex. Further characterization of the substrates of JNK should provide clearer explanations of the intracellular actions of the JNKs and may allow new avenues for targeting the JNK pathways with therapeutic agents downstream of JNK itself.

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A critical role of neural-specific JNK3 for ischemic apoptosis.

Chia-Yi Kuan, Alan J. Whitmarsh, Derek Yang … (2003)

c-Jun N-terminal kinase (JNK) signaling is an important contributor to stress-induced apoptosis, but it is unclear whether JNK and its isoforms (JNK1, JNK2, and JNK3) have distinct roles in cerebral ischemia. Here we show that JNK1 is the major isoform responsible for the high level of basal JNK activity in the brain. In contrast, targeted deletion of Jnk3 not only reduces the stress-induced JNK activity, but also protects mice from brain injury after cerebral ischemia-hypoxia. The downstream mechanism of JNK3-mediated apoptosis may include the induction of Bim and Fas and the mitochondrial release of cytochrome c. These results suggest that JNK3 is a potential target for neuroprotection therapies in stroke.

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Deletion of the c-Jun N-terminal kinase 3 gene protects neonatal mice against cerebral hypoxic-ischaemic injury.

Huseyin Mehmet, G. Pirianov, Katarina G Brywe … (2007)

c-Jun N-terminal kinase 3 (JNK3) is a member of the stress-activated group of mitogen-activated protein kinases. c-Jun N-terminal kinase 3 is a potent mediator of apoptosis and the use of JNK inhibitors or jnk3 gene deletion each protect against brain injury in adults. However, little is known about the role of JNK3 or its mechanism of action in neonatal brain injury. The aim of the present study was to compare the vulnerability of neonatal JNK3 knockout (JNK3 KO) mice and wild-type (WT) mice to cerebral hypoxic-ischaemic injury (HII) using unilateral-carotid occlusion combined with transient hypoxia. The degree of neural tissue loss in JNK3 KO mice was substantially reduced compared with WT mice (JNK3 KO 27.8%+/-2.8% versus WT 48.3%+/-2.0%, P

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Author and article information

Contributors

Guangyi Liu

Jinming Song

Yunliang Guo

Tingting Wang

Zhen Zhou

Journal

Journal ID (nlm-ta): Behav Brain Funct

Journal ID (iso-abbrev): Behav Brain Funct

Title: Behavioral and Brain Functions : BBF

Publisher: BioMed Central

ISSN (Electronic): 1744-9081

Publication date Collection: 2013

Publication date (Electronic): 1 October 2013

Volume: 9

Page: 36

Affiliations

[1 ]Institute of Cerebrovascular Diseases, Affiliated Hospital of Qingdao University Medical College, Qingdao, Shandong 266003, China

Article

Publisher ID: 1744-9081-9-36

DOI: 10.1186/1744-9081-9-36

PMC ID: 3850702

PubMed ID: 24083559

SO-VID: e410e39f-f0d7-4faa-9ba7-c2d60e8a060d

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Astragalus injection protects cerebral ischemic injury by inhibiting neuronal apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats

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Abstract

Background

Methods

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Conclusions

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Neuronal Signaling

Most cited references 12

Uses for JNK: the many and varied substrates of the c-Jun N-terminal kinases.

A critical role of neural-specific JNK3 for ischemic apoptosis.

Deletion of the c-Jun N-terminal kinase 3 gene protects neonatal mice against cerebral hypoxic-ischaemic injury.

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