Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target

Zhou, Haoming; Li, Ning; Yuan, Yuan; Jin, Ya‐Ge; Guo, Haipeng; Deng, Wei; Tang, Qi‐Zhu

doi:10.1007/s00395-018-0698-6

Cited by 92 publications

(64 citation statements)

References 88 publications

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“…In fact, in response to mitochondrial damage, MKP1 has been found to be a protector for the damaged mitochondria. However, this protective factor was significantly inhibited by LPS (Zhou et al, ; Zou et al, ). Therefore, our findings provide further insight into the mechanism of mitochondrial injury induced by the inflammatory response, which also provide a potential target to increase mitochondrial resistance against inflammatory damage.…”

Section: Discussionmentioning

confidence: 99%

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

Huang

Jiang

2019

Journal Cellular Physiology

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MAP kinase phosphatase 1 (MKP1) has been identified as an antiapoptotic protein via sustaining mitochondrial function. However, the role of MKP1 in neuroinflammation has not been fully understood. The aim of this study is to figure out the influence of MKP1 in lipopolysaccharide (LPS)-treated microglia BV-2 cells and investigate whether MKP1 reduces BV-2 cell death via modulating endoplasmic reticulum (ER) stress and mitochondrial dysfunction. The results of this study demonstrated that MKP1 was rapidly downregulated after exposure to LPS. However, the transfection of MKP1 adenovirus could reverse cell viability and attenuate LPS-mediated BV-2 cell apoptosis. Mechanistically, MKP1 overexpression alleviated ER stress and corrected LPS-induced calcium overloading. Besides, MKP1 adenovirus transfection also reversed mitochondrial bioenergetics, maintained mitochondrial membrane potential, and blocked mitochondria-initiated apoptosis signals. Furthermore, we found that MKP1 overexpression is associated with inactivation of mitogen-activated protein kinase-c-Jun N-terminal kinase (MAPK-JNK) pathway. Interestingly, the activation of MAPK-JNK pathway could abolish the protective effects of MKP1 on BV-2 cells survival and mitochondrial function in the presence of LPS. Altogether, our results identified MKP1 as a primary defender of neuroinflammation via modulating ER stress and mitochondrial function in a manner dependent on MAPK-JNK pathway. These findings may open a new window for the treatment of neuroinflammation in the clinical setting. K E Y W O R D S BV-2 cells, ER stress, LPS, mitochondrial damage, MKP1, neuroinflammation

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Section: Discussionmentioning

confidence: 99%

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

Huang

Jiang

2019

Journal Cellular Physiology

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“…Transfection was performed for approximately 48 hours. Then, Western blotting was used to observe the knockdown efficiency after harvesting the transfected cells …”

Section: Methodsmentioning

confidence: 99%

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

Gao

Wang

et al. 2019

Int J Experimental Path

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Summary The pathogenesis of cerebral ischaemia reperfusion injury (IRI) has not been fully described. Accordingly, there is little effective drug available for the treatment of cerebral IRI. The aim of our study was to explore the exact role played by Mfn1‐mediated mitochondrial protection in cerebral IRI and evaluate the beneficial action of resveratrol on reperfused brain. Our study demonstrated that hypoxia‐reoxygenation (HR) injury caused N2a cell apoptosis and this process was highly affected by mitochondrial dysfunction. Decreased mitochondrial membrane potential, increased mitochondrial oxidative stress, and an activated mitochondrial apoptosis pathway were noted in HR‐treated N2a cells. Interestingly, resveratrol treatment could attenuate N2a cell apoptosis via sustaining mitochondrial homeostasis. Further, we found that resveratrol modulated mitochondrial performance via activating the Mfn1‐related mitochondrial protective system. Knockdown of Mfn1 could abolish the beneficial effects of resveratrol on HR‐treated N2a cells. Besides, we also report that resveratrol regulated Mfn1 expression via the AMPK pathway; inhibition of AMPK pathway also neutralized the anti‐apoptotic effect of resveratrol on N2a cells in the setting of cerebral IRI. Taken together our results show that mitochondrial damage is closely associated with the progression of cerebral IRI. In addition we also demonstrate the protective action played by resveratrol on reperfused brain and show that this effect is achieved via activating the AMPK‐Mfn1 pathway.

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“…Finally, the optical density (OD) was measured by a microplate reader at 490 nm. All viability assays were performed in duplicate (H. Zhou, Li, Yuan, et al, 2018); the percentage growth inhibition was calculated using the following formula: Cell viability (%) = (A 490 treatment − A 490 blank )/ (A 490 control − A 490 blank ) × 100 (control: serum-free DMEM with cells; blank: serum-free DMEM without cells) (H. Zhang, Jin, & Faber, 2019).…”

mentioning

confidence: 99%

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

Wang

Zhao

et al. 2019

Journal Cellular Physiology

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Atherosclerosis (AS) is a major pathogenic factor in patients with cardiovascular diseases, and endothelial dysfunction (ED) plays a primary role in the occurrence and development of AS. In our study, we attempted to evaluate the role of phosphatase and tensin homolog (PTEN) in endothelial cell apoptosis under oxidized low-density lipoprotein (ox-LDL) stimulation and identify the associated mechanisms. The results of our study demonstrated that ox-LDL induced human umbilical vein endothelial cell (HUVEC) death via mitochondrial apoptosis, as evidenced by reduced mitochondrial potential, increased mitochondria permeability transition pore opening, cellular calcium overload, and caspase-9/-3 activation. In addition, ox-LDL also suppressed cellular energy production via downregulating the mitochondrial respiratory complex. Moreover, ox-LDL impaired HUVECs migration. Western blot analysis showed that PTEN expression was upregulated after exposure to ox-LDL and knockdown of PTEN could attenuate ox-LDL-mediated endothelial cell damage. Furthermore, we found that ox-LDL impaired mitophagy activity, whereas PTEN deletion could improve mitophagic flux and this effect relied on the activity of the AMPactivated protein kinase (AMPK)-cAMP-response element-binding protein (CREB)-Mitofusin-2 (Mfn2) axis. When the AMPK-CREB-Mfn2 pathway was inhibited, PTEN deletion-associated HUVECs protection was significantly reduced, suggesting that the AMPK-CREB-Mfn2-mitophagy axis is required for PTEN deletion-mediated endothelial cell survival under ox-LDL. Taken together, our results indicate that ox-LDL-induced endothelial cell damage is associated with PTEN overexpression, and inhibition of PTEN could promote endothelial survival via activating the AMPK-CREB-Mfn2-mitophagy signaling pathway. K E Y W O R D S AMPK-CREB-Mfn2 signaling pathway, endothelial cell dysfunction, Mfn2, mitophagy, ox-LDL, PTEN

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Activating transcription factor 3 in cardiovascular diseases: a potential therapeutic target

Cited by 92 publications

References 88 publications

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

MKP1 reduces neuroinflammation via inhibiting endoplasmic reticulum stress and mitochondrial dysfunction

Resveratrol attenuates cerebral ischaemia reperfusion injury via modulating mitochondrial dynamics homeostasis and activating AMPK‐Mfn1 pathway

PTEN inhibition attenuates endothelial cell apoptosis in coronary heart disease via modulating the AMPK–CREB–Mfn2‐mitophagy signaling pathway

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