Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury

Fan, Hong; Tang, Hai‐Bin; Kang, Jianqin; Shan, Lequn; Song, Hong; Zhu, Keqing; Wang, J.; Ju, Gong; Wang, Y.-Z.

doi:10.1016/j.neuroscience.2015.10.049

Cited by 89 publications

(71 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Especially, mitochondrial dysfunction is believed to be an important contributor to SCI [25][26][27]. In addition, ER stress participates in various types of damage after traumatic injury of spinal cord [28][29][30]. In the current study, we found that downregulation of RyR2 significantly ameliorated mitochondrial dysfunction and ER stress, as evidenced by increased oxygen consumption rate and decreased expression of GRP78, ATF3 and ATF6.…”

Section: Discussionsupporting

confidence: 57%

Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress

Liao

Zhang

Sun

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Spinal cord injury (SCI) is a severe health problem worldwide. Ryanodine receptors (RyRs) are a class of intracellular calcium channels in various excitable tissues such as muscles and nervous tissues. The current study was designed to investigate the possible role of RyR2 upregulation in SCI and to elucidate the possible molecular mechanisms. Methods: Rats were injected with LVshRNAi- RyR2 and then exposed to spinal cord contusion injury. Results: The results showed that knockdown of RyR2 significantly promoted the recovery of structural and functional injury in spinal cord, as evidenced by reduction of lesion volume and increase of Basso, Beattie and Bresnahan (BBB) and combined behavioral score (CBS) scores. Knockdown of RyR2 inhibited the increase of proinflammatory cytokines, including IL-1β and TNFα. Moreover, downregulation of RyR2 increased oxygen consumption rate and decreased the expression of glucose-regulated protein 78 (GRP78), activating transcription factor 3 (ATF3) and ATF6, indicating the improvement of mitochondrial dysfunction and endoplasmic reticulum stress after SCI. Furthermore, silence of RyR2 reduced oxidative stress, as reflected by decrease of TBARS and GSSG content and increase of GSH level. The expression of NADPH oxidase 2 (NOX2), NOX4 and p66^shc were increased in SCI rats. Knockdown of RyR2 significantly decreased NOX2 expression, but had no evident effect on NOX4 and p66^shc expression. These results indicated NOX2 may be involved in RyR2-induced ROS generation which mediated contusion-induced spinal cord injury. Conclusion: The data provide novel insights into the mechanism of RyR2-mediated injury and the potential therapeutic targets for injury in spinal cord.

show abstract

Section: Discussionsupporting

confidence: 57%

Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress

Liao

Zhang

Sun

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

show abstract

“…There is no need for approval in all countries. But till today I have no information if any doctor has practiced it [20][21][22][23][24][25].…”

Section: How To Improve the Surgery?mentioning

confidence: 99%

A Mini Review on My Study of the Spinal Cord Injury

Ju¹

2017

J Spine

View full text Add to dashboard Cite

Spinal cord contusion was an injury that had never been effectively treated. The general pathology of the spinal cord contusion had long been studied and published. The major point is that after spinal cord contusion there develops a secondary injury with a necrotic center, which induces gradual expansion of the injury. The logical treatment should be debridment of the necrotic center to terminate further expansion. An early neurosurgery of the spinal cord contusion was designed and practiced clinically. Basically, MRI to determine the level of spinal cord contusion, make a longitudinal incision of the dura mater to expose the injured part of spinal cord. Debride ts necrotic tissue. The operation was followed by intensive rehabilitation for three months. Thirty ASIA-A grade patients were admitted. All the patients resumed certain degree of walk ability. The best result occurred in 13 patients operated 4-14 days after injury (the optimal operation time window). Eleven of the 13 cases were able to walk with a pair of crutches or even to walk without any support.A laboratory of cellular and molecular biology was established to study the mechanism of spinal cord injury. It has an SPF laboratory for making transgenic/knock-out mice, and SPF animal housing rooms with a maximum capacity of 8,000 mice.In all, 103 SCI articles on spinal cord injury have been published.

show abstract

“…[33,34] Our recent studies demonstrated that RIP3 and phosphorylated MLKL are up-regulated in reactive astrocytes and microglia after SCI. [35,36] Reactive astrocytes, which line the spinal cavity, die by M1 microglia/macrophage induced necroptosis partially through toll like receptor/myeloid differentiation 88 signalling. [35] Microglia, the major player of chronic inflammation post-SCI, die through endoplasmic reticulum stress involved necroptosis.…”

Section: Necroptosis and Neurological Diseasesmentioning

confidence: 99%

“…[35] Microglia, the major player of chronic inflammation post-SCI, die through endoplasmic reticulum stress involved necroptosis. [36] These researches raised the straightforward question of how necroptosis regulateschronic inflammation after SCI.…”

Section: Necroptosis and Neurological Diseasesmentioning

confidence: 99%

Necropotosis: a new link between cell death and inflammation

Pan¹,

Liu²,

Liu³

et al. 2016

View full text Add to dashboard Cite

Necroptosis is a type of newly identified cell death induced by apoptotic stimuli under conditions where apoptotic execution is prevented. Studies over the past 10 years have revealed the molecular mechanism of necroptosis and challenged the old conception that necrosis is un-programmed. Recently, more and more data have emerged suggesting a close association between necroptosis and inflammation. In this review, the authors summarized the current knowledge of the mechanism of necroptosis, focusing on tumour necrosis factor α induced necroptosis and the roles of necroptosis in regulating inflammation. In particular, we discussed the occurrence of necroptosis and its relation with inflammation in neurological diseases hoping to provide new insight for the research and treatment of neuroinflammatory disorders.

show abstract

Involvement of endoplasmic reticulum stress in the necroptosis of microglia/macrophages after spinal cord injury

Cited by 89 publications

References 40 publications

Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress

Ryanodine Receptor 2 Plays a Critical Role in Spinal Cord Injury via Induction of Oxidative Stress

A Mini Review on My Study of the Spinal Cord Injury

Necropotosis: a new link between cell death and inflammation

Contact Info

Product

Resources

About