Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling

Huang, Jyun-Bin; Hsu, Shih‐Pin; Pan, Hsiu-Yung; Chen, Shang-Der; Chen, Shu-Fang; Lin, Tay-Jyi; Liu, Xuan-Ping; Li, Jie-Hau; Chen, Nai-Ching; Liou, Chia‐Wei; Hsu, Chia Yang; Chuang, Hung-Yi; Chuang, Yao-Chung

doi:10.3390/ijms21197247

Cited by 19 publications

(13 citation statements)

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“…Repression of PGC-1α and Mfn2 causes a decrease in oxygen consumption, glucose oxidation, and ΔΨm, and an increase in the expression of oxidative phosphorylation proteins ( Chen et al, 2005 ). Moreover, PGC-1α activity is responsive to multiple stimuli, including but not limited to nutrient availability, Ca 2+ , ROS, insulin, estrogen hormone, hypoxia, ATP demand, and cytokines ( Huang et al, 2020 ). Besides PGC-1α, other members of the PGC-1 family of coactivators, namely PGC-1β and PGC-related coactivator (PRC), are also implicated in modulating mitochondrial function, but their exact role is not well understood ( Scarpulla, 2008 ).…”

Section: Oxidative Stress and Mitochondrial Defects In Admentioning

confidence: 99%

Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease

Misrani

Tabassum

Yang

2021

Front. Aging Neurosci.

297

174

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Mitochondria play a pivotal role in bioenergetics and respiratory functions, which are essential for the numerous biochemical processes underpinning cell viability. Mitochondrial morphology changes rapidly in response to external insults and changes in metabolic status via fission and fusion processes (so-called mitochondrial dynamics) that maintain mitochondrial quality and homeostasis. Damaged mitochondria are removed by a process known as mitophagy, which involves their degradation by a specific autophagosomal pathway. Over the last few years, remarkable efforts have been made to investigate the impact on the pathogenesis of Alzheimer’s disease (AD) of various forms of mitochondrial dysfunction, such as excessive reactive oxygen species (ROS) production, mitochondrial Ca2+ dyshomeostasis, loss of ATP, and defects in mitochondrial dynamics and transport, and mitophagy. Recent research suggests that restoration of mitochondrial function by physical exercise, an antioxidant diet, or therapeutic approaches can delay the onset and slow the progression of AD. In this review, we focus on recent progress that highlights the crucial role of alterations in mitochondrial function and oxidative stress in the pathogenesis of AD, emphasizing a framework of existing and potential therapeutic approaches.

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Section: Oxidative Stress and Mitochondrial Defects In Admentioning

confidence: 99%

Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease

Misrani

Tabassum

Yang

2021

Front. Aging Neurosci.

297

174

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“…VEGF-A, one of the five members in the VEGF family, shows the highest specificity and the strongest physiological effects (Harper and Bates 2008;Rennel et al 2008). VEGF directly interacts with mitogens in endothelial cells and thus promotes the permeability of blood vessels, increases blood oxygen supply, and enhances the proliferation of vascular endothelial cells (Huang et al 2020;Song and Finley 2020). Inhibition of extracellular signal-regulated kinase (ERK)-MAPK signaling by PD98059 significantly increased cardiomyocyte apoptosis, caspase 3 activity, and the myocardial defect area, and the effects on apoptosis could be reversed by the administration of fasudil (a Rho kinase inhibitor) (Czabotar et al 2014).…”

Section: Introductionmentioning

confidence: 99%

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway

Wang

Zou

Liu

et al. 2021

In Vitro Cell.Dev.Biol.-Animal

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Enhanced apoptosis of cardiomyocytes in suffering overloaded saturated fatty acids (SFAs) can result in myocardial infarction and cardiac dysfunction. The function of vascular endothelial growth factor (VEGF) in cardiomyocyte protection was not clearly described. To investigate the preservative effects of VEGF sensitization on ceramide-mediated programmed cell death of cardiomyocytes, palmitate-induced injury in H9c2 cells was established as an in vitro model. Results revealed that 0.5 mM palmitate application effectively led to debased viability and activated apoptotic factors. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h of treatment with 0.5 mM PAL. In addition, cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. Reduced apoptosis rate and expression of caspase 3, Bax, and NF-κB p65 were observed in this process, while boosted Bcl-2, p-JNK/JNK expression and activity of caspase 3 were checked. However, p-ERK/ERK levels did not exhibit a significant change. These findings indicated the protective effects of VEGF in confronting the ceramide-induced cardiomyocyte apoptosis, and would devote therapeutic targets for cardiovascular safeguard in dealing with fatty acid stress.

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“…VEGF-A, one of the ve members in the VEGF family, shows the highest speci city and the strongest physiological effects (23,24). VEGF directly interacts with mitogens in endothelial cells and thus promotes the permeability of blood vessels, increases blood oxygen supply, and enhances the proliferation of vascular endothelial cells (25,26). Inhibition of extracellular signal regulated kinase (ERK)-MAPK signaling by PD98059 signi cantly increased cardiomyocyte apoptosis, caspase 3 activity, and the myocardial defect area, and the effects on apoptosis could be reversed by the administration of fasudil (a Rho kinase inhibitor) [38].…”

Section: Introductionmentioning

confidence: 99%

Vascular Endothelial Growth Factor Ameliorated Palmitate Induced Cardiomyocyte Injury via JNK Pathway

Wang

Zou

Liu³

et al. 2020

Preprint

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Objective To investigate the effect of palmitate (PAL) on apoptosis and the timing and activity of VEGF expression in HHHM2 myocardial cells (a human embryonic cardiomyocyte cell- line). Methods 1. Cardiomyocytes were divided into the following five groups: the control group and the 0.2 mM, 0.5 mM, 0.8 mM, and 1.2 mM PAL groups. We examined the changes in cell viability by MTT assay after PAL incubation for 24 h and the cardiomyocyte apoptosis rate by FACS examination, and thus determined the effective concentration of PAL. The transcription levels of CASP3, Bcl-2, Bax, and VEGF were detected by quantitative fluorescence PCR and the protein expression of caspase 3 and VEGF by western blot. 2. To observe the time-dependent effects on cell injury induced by 0.5 mM PAL, cardiomyocytes were divided into 0, 4, 8, 16, 24, and 48 h groups. The variation in cell viability was examined by MTT assay. The transcription levels of CASP3, Bcl-2, Bax, and VEGF were detected by quantitative fluorescence PCR and the protein expression of caspase 3 and VEGF by western blot. 3. To observe the effects of VEGF on the PAL induced apoptosis of cardiomyocytes, the cells were divided into the control group and the VEGF overexpression group. At 24 h after transfection, cells were incubated with 0.5 mM PAL for 6, 12, 24, and 48 h. Cell viability was examined by MTT assay. The apoptosis rate was measured by FACS using the Annexin V-FITC kit. The transcription levels of CASP3, Bcl-2, Bax, NF-kB p65, and VEGF were measured by quantitative fluorescence PCR, the protein expression of VEGF, caspase 3, Bcl-2, Bax, NF-κB p65, p-JNK/JNK, and p-ERK/ERK were measured by western blot, as well as caspase 3 activity. Results 1. A dose-dependent relation between the concentration of PAL and H9c2 cardiomyocyte injury was observed. In the 0.5 mM group, the apoptosis rate was increased significantly, while cell viability was decreased, indicating that 0.5 mM PAL was the ideal concentration to induce cardiomyocyte apoptosis. The expression of caspase 3 and Bax was significantly increased, and the expression of VEGF was enhanced, while the levels of Bcl-2 remained unchanged during the process. 2. A significant time-dependent relation between PAL and cardiomyocyte injury was observed. The apoptosis rate was increased greatly after 16 h treatment with 0.5 mM PAL. 3. Cell viability was restored by VEGF overexpression during treatment with 0.5 mM PAL. The apoptosis rate was also reduced by VEGF overexpression, as detected by FACS. The expression of caspase 3, Bax, and NF-κB p65 was significantly decreased, Bcl-2 and VEGF expression was dramatically increased, p-JNK/JNK expression was significantly enhanced, p-ERK/ERK levels did not exhibit a significant change, and the activity of caspase 3 was significantly decreased. Conclusions 1. PAL can induce injury and apoptosis in HHHM2 myocardial cells, and these effects are time-dependent. A PAL concentration of 0.5 mM was ideal to establish the cardiac cell injury model. 2. PAL at a concentration of 0.5 mM can effectively induce cardiomyocyte injury and enhance the expression of caspase 3, Bax, and VEGF, especially after 24 h and 48 h of PAL treatment. 3. VEGF overexpression can reverse the effects of PAL on apoptosis and cell viability. In addition, VEGF overexpression inhibited the expression of proapoptotic and inflammatory factors, caspase 3 activity, and transduction of the MAPK signaling pathway.

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Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling

Cited by 19 publications

References 85 publications

Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease

Mitochondrial Dysfunction and Oxidative Stress in Alzheimer’s Disease

Vascular endothelial growth factor ameliorated palmitate-induced cardiomyocyte injury via JNK pathway

Vascular Endothelial Growth Factor Ameliorated Palmitate Induced Cardiomyocyte Injury via JNK Pathway

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