Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38

Kasuya, Yoshitoshi; Umezawa, Hiroki; Hatano, Masahiko

doi:10.3390/ijms19030867

Cited by 45 publications

(40 citation statements)

References 87 publications

(108 reference statements)

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“…Inflammation is a main contributor of the secondary injury of SCI, in which lots of signalling pathways are involved. In central nervous system, several stimuli such as LPS can induce the activation of NF-jB and JNK pathways [30,31]. The activated signalling triggers the production of proinflammatory cytokines and thereby induces inflammatory response and increases vulnerability to apoptosis [32,33].…”

Section: Discussionmentioning

confidence: 99%

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 lg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1b, IL-6, IL-8 and TNF-a evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-jB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-jB and JNK pathways. HIGHLIGHTS 1. Geniposide prevents LPS-induced injury in PC12 cells; 2. Geniposide up-regulates miR-145-5p; 3. Geniposide protects PC12 cells via up-regulation of miR-145-5p; 4. Geniposide inhibits NF-jB and JNK pathways via up-regulation of miR-145-5p.

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Section: Discussionmentioning

confidence: 99%

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…These findings indicate that ERK is not inhibited by RHL in spinal cord tissues after SCI. Previous study has also shown that JNK1/2 was involved in response to stress stimuli . Hence, we also evaluated the effects of RHL on JNK1/2 phosphorylation.…”

Section: Resultsmentioning

confidence: 94%

“…Next, we evaluated the underlying mechanism by which RHL can improve functional recovery and promote neuroprotection after SCI. By affecting gene transcription and regulation in animal cells, the MAPK family influences cell proliferation, differentiation, transformation and apoptosis, including ERK1/2 MAPK family, the p38 MAPK family and JNK1/2 . In various cancer cells, activation of ERK is reported to enhance cell proliferation .…”

Section: Resultsmentioning

confidence: 99%

“…By affecting gene transcription and regulation in animal cells, the MAPK family influences cell proliferation, differentiation, transformation and apoptosis, including ERK1/2 MAPK family, the p38 MAPK family and JNK1/2. 13,36 In various cancer cells, activation of ERK is reported to enhance cell proliferation. 37,38 Here, our data showed that ERK phosphorylation was significantly enhanced after SCI, but RHL treatment could not suppress the activation of ERK.…”

Section: Discussionmentioning

confidence: 99%

“…Previous study has also shown that JNK1/2 was involved in response to stress stimuli. 36 Hence, we also evaluated the effects of RHL on JNK1/2 phosphorylation. Our data showed that RHL could not inhibit JNK activation.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Hao

Wang

Daiping

et al. 2019

The Kaohsiung J of Med Scie

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The current study aims to investigate the effect of rhein lysinate (RHL) on neuromotor function in rats with spinal cord injury (SCI) and to explore the underlying mechanism. A total of 63 adult male SD rats were randomly divided into the sham group, SCI group and RHL group (SCI‐RHL group), with 21 rats in each group. Basso Beattie Bresnahan (BBB) scoring and the inclined plate test were used to evaluate the changes in motor function after SCI. Then, superoxide dismutase (SOD), glutathione peroxidase (GSH‐Px), and malondialdehyde (MDA) contents were quantified. Caspase‐3‐positive cells in spinal cord tissue were detected by immunohistochemical (IHC) staining, and protein expression was detected by Western blots. Here, our data showed that compared with the SCI group, the BBB score and inclined plate test score of the SCI‐RHL group were significantly higher than those of the SCI group 7 days after the RHL intervention. After 7 days of RHL treatment, the activities of SOD and GSH‐Px in the spinal cord increased significantly. At the same time, RHL reduced the MDA content in spinal cord tissue of SCI rats. Moreover, cleaved‐caspase‐3‐positive cells and apoptotic cells were significantly lower in the SCI‐RHL group than in the SCI group. More importantly, p38 mitogen‐activated protein kinase (p38 MAPK) was significantly decreased in the SCI‐RHL group compared with the SCI group. In summary, RHL can inhibit the activation of the p38 MAPK pathway after SCI, thereby reducing the apoptosis of spinal cord neurons and improving the neuromotor function of SCI rats.

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Pulsed electromagnetic field and relief of hypoxia‐induced neuronal cell death: The signaling pathway

Gessi

Merighi

Bencivenni

et al. 2019

Journal Cellular Physiology

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Low‐energy low‐frequency pulsed electromagnetic fields (PEMFs) exert several protective effects, such as the regulation of kinases, transcription factors as well as cell viability in both central and peripheral biological systems. However, it is not clear on which bases they affect neuroprotection and the mechanism responsible is yet unknown. In this study, we have characterized in nerve growth factor‐differentiated pheochromocytoma PC12 cells injured with hypoxia: (i) the effects of PEMF exposure on cell vitality; (ii) the protective pathways activated by PEMFs to relief neuronal cell death, including adenylyl cyclase, phospholipase C, protein kinase C epsilon and delta, p38, ERK1/2, JNK1/2 mitogen‐activated protein kinases, Akt and caspase‐3; (iii) the regulation by PEMFs of prosurvival heat‐shock proteins of 70 (HSP70), cAMP response element‐binding protein (CREB), brain‐derived neurotrophic factor (BDNF), and Bcl‐2 family proteins. The results obtained in this study show a protective effect of PEMFs that are able to reduce neuronal cell death induced by hypoxia by modulating p38, HSP70, CREB, BDNF, and Bcl‐2 family proteins. Specifically, we found a rapid activation (30 min) of p38 kinase cascade, which in turns enrolles HSP70 survival chaperone molecule, resulting in a significant CREB phosphorylation increase (24 hr). In this cascade, later (48 hr), BDNF and the antiapoptotic pathway regulated by the Bcl‐2 family of proteins are recruited by PEMFs to enhance neuronal survival. This study paves the way to elucidate the mechanisms triggered by PEMFs to act as a new neuroprotective approach to treat cerebral ischemia by reducing neuronal cell death.

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Stress-Activated Protein Kinases in Spinal Cord Injury: Focus on Roles of p38

Cited by 45 publications

References 87 publications

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p

Rhein lysinate improves motor function in rats with spinal cord injury via inhibiting p38 MAPK pathway

Pulsed electromagnetic field and relief of hypoxia‐induced neuronal cell death: The signaling pathway

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