MSK1 downregulation is associated with neuronal and astrocytic apoptosis following subarachnoid hemorrhage in rats

Niu, Bo; Guo, Geng; Liu, Hong; Ning, Lei; Sun, Bo; Li, Zhen; Wang, Shuo; Lv, Zhengwen; Fan, Cundong

doi:10.3892/ol.2017.6496

Cited by 7 publications

(7 citation statements)

References 30 publications

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“…TXNIP, an endogenous inhibitor of the Trx system, directly binds to Trx1/Trx2 and inhibits their activity through disulfide exchange (Yoshihara et al, 2014;Nasoohi et al, 2018). The inhibition or the deletion of TXNIP is found to be neuroprotective in cerebrovascular and neurodegenerative diseases (Nasoohi et al, 2018). In the present study, the Trx/TXNIP system was involved in the antioxidative mechanism of Bak during EBI.…”

Section: Discussionmentioning

confidence: 57%

“…Previously, it was believed that the apoptosis mainly occurred on neurons after stroke. However, the latest research showed that the apoptosis and cell loss also occurred on glial cells (Chen et al, 2017;Ma et al, 2017;Ning et al, 2017;Sekerdag et al, 2018). Strictly, TUNEL staining alone could not reflect the entire destruction of neurons.…”

Section: Discussionmentioning

confidence: 99%

“…Trx1, which is located mainly in the cytoplasm, is usually induced as a response to oxidative stresses (Yoshihara et al, 2014). TXNIP, an endogenous inhibitor of the Trx system, directly binds to Trx1/Trx2 and inhibits their activity through disulfide exchange (Yoshihara et al, 2014;Nasoohi et al, 2018). The inhibition or the deletion of TXNIP is found to be neuroprotective in cerebrovascular and neurodegenerative diseases (Nasoohi et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Liu

Guo

et al. 2020

Front. Pharmacol.

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Subarachnoid hemorrhage (SAH) is a fatal cerebrovascular condition with complex pathophysiology that reduces brain perfusion and causes cerebral functional impairments. An increasing number of studies indicate that early brain injury (EBI), which occurs within the first 72 h of SAH, plays a crucial role in the poor prognosis of SAH. Bakuchiol (Bak) has been demonstrated to have multiorgan protective effects owing to its antioxidative and anti-inflammatory properties. The present study was designed to investigate the effects of Bak on EBI after SAH and its underlying mechanisms. In this study, 428 adult male C57BL/6J mice weighing 20 to 25 g were observed to investigate the effects of Bak administration in an SAH animal model. The neurological function and brain edema were assessed. Content of MDA/3-NT/8-OHdG/superoxide anion and the activity of SOD and GSH-Px were tested. The function of the blood-brain barrier (BBB) and the protein levels of claudin-5, occludin, zonula occludens-1, and matrix metalloproteinase-9 were observed. TUNEL staining and Fluoro-Jade C staining were conducted to evaluate the death of neurons. Ultrastructural changes of the neurons were observed under the transmission electron microscope. Finally, the roles of Trx, TXNIP, and AMPK in the protective effect of Bak were investigated. The data showed that Bak administration 1) increased the survival rate and alleviated neurological functional deficits; 2) alleviated BBB disruption and brain edema; 3) attenuated oxidative stress by reducing reactive oxygen species, MDA, 3-NT, 8-OHdG, gp91 phox , and 4-HNE; increased the activities of SOD and GSH-Px; and alleviated the damage to the ultrastructure of mitochondria; 4) inhibited cellular apoptosis by regulating the protein levels of Bcl-2, Bax, and cleaved caspase-3; and 5) upregulated the protein levels of Trx1 as well as the phosphorylation of AMPK and downregulated the protein levels of TXNIP. Moreover, the protective effects of Bak were partially reversed by PX-12 and compound C. To summarize, Bak attenuates EBI after SAH by alleviating BBB disruption, oxidative

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Liu

Guo

et al. 2020

Front. Pharmacol.

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“…Recent research has also shown that MSK1 might be involved in SAH and TBI-induced apoptosis. (Ning et al 2013, 2017). However, whether it is related to neuronal apoptosis caused by SCI was not clear.…”

Section: Discussionmentioning

confidence: 99%

“…In the CNS (central nervous system), MSK1 is involved in astrocyte inflammation and inhibits the production of inflammatory cytokines (Gong et al 2013); moreover, it might be involved in the pathophysiology of traumatic brain injury (TBI) (Ning et al 2013). MSK1 was also suggested to contribute to SAH (subarachnoid hemorrhage)-induced apoptosis (Ning et al 2017). Further, recent research has demonstrated its expression in the spinal cord (Li et al 2013), but its specific role in spinal cord injury is still not clear.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

et al. 2019

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Mitogen- and stress-activated kinase (MSK) 1 is a nuclear serine/threonine kinase. In the central nervous system, it plays an important role in regulating cell proliferation and neuronal survival; it is also involved in astrocyte inflammation and the inhibition of inflammatory cytokine production. However, its specific role in spinal cord injury is not clear. Here, we aimed to elucidate this role using an in vivo animal model. In this study, we found that MSK1 is gradually decreased, starting 1 day after spinal cord injury and to its lowest level 3 days post-injury, after which it gradually increased. To further investigate the possible function of MSK1 in spinal cord injury, we interfered with its expression by utilizing a small interfering RNA (siRNA)-encoding lentivirus, which was injected into the injured spinal cord to inhibit local expression. After MSK1 inhibition, we found that the expression of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1β were increased. Moreover, the expression of IL-10 was decreased. In addition, neuronal apoptotic cells were increased significantly and expression of the apoptosis-related protein caspase-3 was also increased. Ultrastructural analysis of nerve cells also revealed typical neuronal apoptosis and severe neuronal damage. Finally, we found that hindlimb motor function decreased significantly with MSK1 knockdown. Therefore, our findings suggest that the inhibition of this protein promotes inflammatory responses and apoptosis and suppresses functional recovery after spinal cord injury. MSK1 might thus play an important role in repair after spinal cord injury by regulating inflammation and apoptosis. Electronic supplementary material The online version of this article (10.1007/s12031-019-01298-9) contains supplementary material, which is available to authorized users.

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Protective Effect of Mitogen- and Stress-Activated Protein Kinase on the Rats with Focal Ischemia-Reperfusion Injury

Zhou

Gao

et al. 2019

Inflammation

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MSK1 downregulation is associated with neuronal and astrocytic apoptosis following subarachnoid hemorrhage in rats

Cited by 7 publications

References 30 publications

Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice

Inhibition of MSK1 Promotes Inflammation and Apoptosis and Inhibits Functional Recovery After Spinal Cord Injury

Protective Effect of Mitogen- and Stress-Activated Protein Kinase on the Rats with Focal Ischemia-Reperfusion Injury

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