Phosphorylation of p38 MAPK mediates aquaporin 9 expression in rat brains during permanent focal cerebral ischaemia

Wei, Xiaoyü; Ren, Xüxia; Jiang, Rong; Li, Hui; Gao, Fei; Chen, Yuqin; Hou, Jiaojiao; Liu, Xueyuan; Sun, Shanquan; Yang, Mei

doi:10.1007/s10735-015-9618-3

Cited by 15 publications

(13 citation statements)

References 27 publications

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“…Therapies targeting inflammation, oxidative stress or cardiac dysfunction induced by CO poisoning have been proved effective in animal models, suggesting a great potential of "downstream-targeting" treatment in CO poisoning. Regulation of AQPs by p38-MAPK pathway activation has been demonstrated in hyperosmotic 50 and ischaemic conditions, 8 both of which highlighted the role of cerebral oedema in the pathogenesis of encephalopathy. In this study, we demonstrated for the first time that AQP1 and AQP4 were involved in the cerebral oedema caused by acute CO exposure in rat models, and p38 MAPK inhibitor, SB203580 effectively reduced cerebral oedema and alleviated associated AQP1 and AQP4 up-regulation, suggesting the manipulation of AQP1 and AQP4 could be another "downstream-targeting" treatment of acute CO poisoning.…”

Section: Discussionmentioning

confidence: 99%

“…Approximately 15%–49% of patients that recovered from acute CO poisoning developed neurocognitive sequelae, and around 0.2%–47% of patients developed delayed neuropsychological sequelae after 2‐6 weeks of CO poisoning . Effective antidotal therapy is not available at present, and hyperbaric oxygen therapy (HBO 2 ) is the best treatment that physicians can offer . Therefore, comprehensive understanding of the pathogenesis of this disease is the key to the search of novel therapeutic strategies.…”

Section: Introductionmentioning

confidence: 99%

“…7 Effective antidotal therapy is not available at present, and hyperbaric oxygen therapy (HBO 2 ) is the best treatment that physicians can offer. 8 Therefore, comprehensive understanding of the pathogenesis of this disease is the key to the search of novel therapeutic strategies.…”

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confidence: 99%

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Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes

Jia

Chen

et al. 2019

Basic Clin Pharma Tox

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Cerebral oedema is a major pathological change of acute carbon monoxide (CO) poisoning, the pathogenesis of which is still unclear. In the aquaporin (AQP) water channel family, AQP1 and AQP4 play critical roles in the progress of cerebral oedema of various neuropathological events. However, their functions in CO poisoning have not been demonstrated. In this study, we investigated the expressions of AQPs and associated mechanisms of brain injury in an acute CO poisoning rat model. Compared with the control injected intraperitoneally with equal volume of air, the dry weight/wet weight (DW/WW) ratio of brain water content, levels of AQP1, AQP4, phosph‐p38 mitogen‐activated protein kinase (p‐p38 MAPK) and astrocyte marker, glial fibrillary acidic protein (GFAP) in the frontal cortex and hippocampal CA1 of acute CO poisoning group significantly increased at 6, 12, 24 hours after CO injection. Intracerebroventricular injection with a p38 MAPK inhibitor, SB203580 (200 µmol/L/kg/d), before CO injection reduced water content in the brain tissues and significantly decreased levels of AQP1, AQP4, p‐p38 MAPK and GFAP. Therefore, our study showed that the overexpressions of AQP1 and AQP4 were involved in the development of CO poisoning‐induced cerebral oedema, which could be attenuated by inhibition of p‐p38 MAPK signalling. Manipulation of AQPs and p38 MAPK may be a new therapeutic strategy for acute CO poisoning.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes

Jia

Chen

et al. 2019

Basic Clin Pharma Tox

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“…JNK, p38MAPK, and MEK inhibitors SP600125, SB203580, and PD98059 (10 pmol, Santa Cruz Biotechnology, Santa Cruz, CA) were dissolved by 5μL PBS (Tu et al, 2015; Wei et al, 2015; Yatsushige et al, 2008) (5μL PBS served as the vehicle control). Those inhibitors were injected at 20 min before SAH.…”

Section: Methodsmentioning

confidence: 99%

Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats

et al. 2016

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Background and Purpose Since tozasertib is neuroprotective for injured optic nerve, this study is intended to test whether tozasertib reduces early brain injury after subarachnoid hemorrhage (SAH) in a rat model. Methods One hundred fifty-five (155) male Sprague-Dawley rats were randomly subjected to endovascular perforation model of SAH and sham group. SAH grade, neurological score, and brain water content were measured at 24 and 72 hours after SAH. Dual leucine zipper kinase (DLK) and its downstream factors, JNK-interacting protein 3 (JIP3), MA2K7, p-JNK/JNK (c-Jun N-terminal kinase), and apoptosis related proteins cleaved caspase-3 (CC-3), Bim, Bcl-2, and cleaved caspase-9 (CC-9) were analyzed by western blot at 24 hours after SAH. Apoptotic cells were detected by terminal deoxynucleotid transferase-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL). DLK small interfering RNA (siRNA), JIP3 siRNA and MA2K7 siRNA, the JNK, p38MAPK, and MEK inhibitors SP600125, SB203580, and PD98059 were used for intervention. Results Tozasertib reduced neuronal apoptosis, attenuated brain edema and improved neurobehavioral deficits 24 and 72 hours after SAH. At 24 hours After SAH, DLK/JIP3/MA2K7/p-JNK/CC-3 expressions were elevated markedly and tozasertib reduced DLK, MA2K7/p-JNK/CC-3 expressions but enhanced JIP3 expression. In the presence of tozasertib, DLK/JIP3/MA2K7 siRNA and SP600125, SB203580 and PD98059 deteriorated the neurobehavioral deficits, brain edema and increased the expression of CC-3. SAH potentiated the expression of Bim, CC-9, and CC-3 but reduced Bcl-2, while tozasertib reduced expression of Bim, CC-9, and CC-3 but enhanced Bcl-2. Conclusions Tozasertib reduced neuronal apoptosis and improved outcome possibly via DLK/JIP3/MA2K7/JNK pathways after SAH.

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“…The core of the MAPK pathway comprises the following sequences: c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinases ½ (ERK1/2), and p38 kinase (p38) [11]. Previous studies, including those conducted in the same lab, have proven that p38 MAPK regulates the AQP9 expression in astrocytes under hyperosmotic condition [12] or ischemia [13]. However, no study has determined whether the changes in the AQP9 expression are related to the MAPK signal pathway under different hyperglycemia conditions.…”

Section: Introductionmentioning

confidence: 99%

Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus

Hou

Ren

et al. 2018

Horm Metab Res

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Aquaporin-9 (AQP9) is an aquaglyceroporin that biophysically conducts water, glycerol, and other small solutes. AQP9 is expressed in hepatocytes on the sinusoidal surfaces of hepatocyte plates in the liver, where it is considered responsible for the glycerol uptake in gluconeogenesis. However, limited information is available on the expression and regulating mechanism of AQP9 in different hyperglycemia models. Thus, this study examined the expression patterns of AQP9 and mitogen-activated protein kinase (MAPK) in Types 1 and 2 diabetes mellitus (DM) to clarify the roles and regulating mechanism of AQP9 in gluconeogenesis. Compared with the control group, the AQP9 expression significantly increased in both Types 1 and 2 DM, and the increased expression was associated with the activation of phosphorylated JNK (p-JNK) and the inhibition of phosphorylated p38 (p-p38). By contrast, phosphorylated ERK remained stable in the liver with Type 1 or 2 DM. These effects could be reversed by insulin treatment. That is, insulin downregulated AQP9 by inhibiting p-JNK and activating p-p38. The upregulation of AQP9 could be involved in gluconeogenesis and co-regulated by the JNK and p38 MAPK pathway in both Types 1 and 2 DM.

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Phosphorylation of p38 MAPK mediates aquaporin 9 expression in rat brains during permanent focal cerebral ischaemia

Cited by 15 publications

References 27 publications

Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes

Involvement of p38 mitogen‐activated protein kinase in altered expressions of AQP1 and AQP4 after carbon monoxide poisoning in rat astrocytes

Tozasertib attenuates neuronal apoptosis via DLK/JIP3/MA2K7/JNK pathway in early brain injury after SAH in rats

Similar Aquaporin9 and MAPK Expression Profiles in the Liver of Types 1 and 2 Diabetes Mellitus

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