Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Wang, Yunlong; Zhang, Aihua; Lu, Shulai; Pan, Xinting; Jia, Dongmei; Yu, Wenjuan; Jiang, Yanxia; Li, Xinde; Wang, Xuefeng; Zhang, Jidong; Hou, Lin; Sun, Ying

doi:10.1016/j.intimp.2014.09.002

Cited by 14 publications

(8 citation statements)

References 39 publications

(43 reference statements)

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“…Previous studies indicated that activation of MAPKs signaling promoted the progression of ARDS17, but the functional linkage of the MAPKs pathways with ACE2/Ang-(1-7)/Mas signaling axis in LPS-induced lung injury has not been elucidated. Our current study showed that LPS administration stimulated the phosphorylation of P38 MAPK, ERK1/2 and JNK, which was significantly reduced by ACE2 overexpression in lung tissue.…”

Section: Discussionmentioning

confidence: 99%

“…The phosphorylation levels of p38 MAPK, extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) are all significantly increased in LPS-induced lung injury17. Consequently, inhibition of p38 MAPK or ERK efficiently attenuates LPS-induced pulmonary inflammatory response1819.…”

mentioning

confidence: 99%

“…Previous studies have showed that the activation of mitogen-activated protein kinases (MAPKs) pathway is associated with the process of ARDS. The phosphorylation levels of p38 MAPK, extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) are all significantly increased in LPS-induced lung injury 17 . Consequently, inhibition of p38 MAPK or ERK efficiently attenuates LPS-induced pulmonary inflammatory response 18 19 .…”

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confidence: 99%

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Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways

Zeng

Cao

et al. 2016

Sci Rep

140

124

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Acute respiratory distress syndrome (ARDS) caused by severe sepsis remains a major challenge in intensive care medicine. ACE2 has been shown to protect against lung injury. However, the mechanisms of its protective effects on ARDS are largely unknown. Here, we report that ACE2 prevents LPS-induced ARDS by inhibiting MAPKs and NF-κB signaling pathway. Lentiviral packaged Ace2 cDNA or Ace2 shRNA was intratracheally administrated into the lungs of male SD rats. Two weeks after gene transfer, animals received LPS (7.5 mg/Kg) injection alone or in combination with Mas receptor antagonist A779 (10 μg/Kg) or ACE2 inhibitor MLN-4760 (1 mg/Kg) pretreatment. LPS-induced lung injury and inflammatory response were significantly prevented by ACE2 overexpression and deteriorated by Ace2 shRNA. A779 or MLN-4760 pretreatment abolished the protective effects of ACE2. Moreover, overexpression of ACE2 significantly reduced the Ang II/Ang-(1-7) ratio in BALF and up-regulated Mas mRNA expression in lung, which was reversed by A779. Importantly, the blockade of ACE2 on LPS-induced phosphorylation of ERK1/2, p38 and p50/p65 was also abolished by A779. Whereas, only the ERK1/2 inhibitor significantly attenuated lung injury in ACE2 overexpressing rats pretreated with A779. Our observation suggests that AEC2 attenuates LPS-induced ARDS via the Ang-(1-7)/Mas pathway by inhibiting ERK/NF-κB activation.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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confidence: 99%

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Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways

Zeng

Cao

et al. 2016

Sci Rep

140

124

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“…The NF–κB cascade is pivotal to the intracellular signaling pathway involved in apoptosis and the inflammatory response, and activation of NF–κB is central to the regulation of pulmonary inflammation and involved in the pathogenesis of ARDS 42 43 44 . LPS–induced lung injury is associated with activation of MAPKs and NF–κB signaling pathways 47 ; the inhibition of ERK or p38 protects against LPS–induced lung injury by inhibiting the NF–kB pathway 28 48 . Pretreatment with Ang–(1–7) prevents AngII–induced lung fibroblast apoptotic resistance by inhibiting the MAPK/NF–kB pathway 49 .…”

Section: Discussionmentioning

confidence: 99%

Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways

Cao

Zeng

et al. 2015

Sci Rep

104

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ACE2 and Ang–(1–7) have important roles in preventing acute lung injury. However, it is not clear whether upregulation of the ACE2/Ang–(1–7)/Mas axis prevents LPS–induced injury in pulmonary microvascular endothelial cells (PMVECs) by inhibiting the MAPKs/NF–κB pathways. Primary cultured rat PMVECs were transduced with lentiviral–borne Ace2 or shRNA–Ace2, and then treated or not with Mas receptor blocker (A779) before exposure to LPS. LPS stimulation resulted in the higher levels of AngII, Ang–(1–7), cytokine secretion, and apoptosis rates, and the lower ACE2/ACE ratio. Ace2 reversed the ACE2/ACE imbalance and increased Ang–(1–7) levels, thus reducing LPS–induced apoptosis and inflammation, while inhibition of Ace2 reversed all these effects. A779 abolished these protective effects of Ace2. LPS treatment was associated with activation of the ERK, p38, JNK, and NF–κB pathways, which were aggravated by A779. Pretreatment with A779 prevented the Ace2–induced blockade of p38, JNK, and NF–κB phosphorylation. However, only JNK inhibitor markedly reduced apoptosis and cytokine secretion in PMVECs with Ace2 deletion and A779 pretreatment. These results suggest that the ACE2/Ang–(1–7)/Mas axis has a crucial role in preventing LPS–induced apoptosis and inflammation of PMVECs, by inhibiting the JNK/NF–κB pathways.

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“… 87 It might be that the activity of BAG2 is also dependent upon temperature sensitive kinases like p38 and ERK1/2. 102 which would render it inactive under cold conditions. Thus, the regulation of levels of phosphorylated Tau in more-plastic, less-differentiated neurons is more dependent upon degradation by BAG2, than in more-differentiated less-plastic neurons ( Fig.…”

Section: Temperature Tau and Alzheimer's Diseasementioning

confidence: 99%

Temperature and toxic Tau in Alzheimer's disease: new insights

et al. 2015

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Alzheimer's disease (AD), the most common dementia in the elderly, is characterized by cognitive impairment and severe autonomic symptoms such as disturbance in core body temperature (Tc), which may be predictors or early events in AD onset. Inclusions of phosphorylated Tau (p-Tau) are a hallmark of AD and other neurodegenerative disorders called “Tauopathies.” Animal and human studies show that anesthesia augments p-Tau levels through reduction of Tc, with implications for AD. Additionally, hypothermia impairs memory and cognitive function. The molecular networks related to Tc that are associated with AD remain poorly characterized. Under physiological conditions, Tau binds microtubules, promoting their assembly and stability. The dynamically regulated Tau-microtubule interaction plays an important role in structural remodeling of the cytoskeleton, having important functions in neuronal plasticity and memory in the hippocampus. Hypothermia-induced increases in p-Tau levels are significant, with an 80% increase for each degree Celsius below normothermic conditions. Although the effects of temperature on Tau phosphorylation are evident, its effects on p-Tau degradation remain poorly understoodWe review information concerning the mechanisms of Tau regulation of neuron plasticity via its effects on microtubule dynamics, with focus on pathways regulating the abundance of phosphorylated Tau species. We highlight the effects of temperature on molecular mechanisms influencing the development of Tau-related diseases. Specifically, we argue that cold might preferentially affects central nervous system structures that are highly reliant upon plasticity, such as the hippocampus, and that the effect of cold on Tau phosphorylation may constitute a pathology-initiating trigger leading to neurodegeneration.

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Adenosine 5′-monophosphate-induced hypothermia inhibits the activation of ERK1/2, JNK, p38 and NF-κB in endotoxemic rats

Cited by 14 publications

References 39 publications

Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways

Angiotensin-converting enzyme 2 prevents lipopolysaccharide-induced rat acute lung injury via suppressing the ERK1/2 and NF-κB signaling pathways

Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis prevents lipopolysaccharide–induced apoptosis of pulmonary microvascular endothelial cells by inhibiting JNK/NF–κB pathways

Temperature and toxic Tau in Alzheimer's disease: new insights

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