Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells

Sriwastva, Mukesh K.; Kunjunni, Remesh; Andrabi, Mutahar; Prasad, Kameshwar; Saxena, Renu; Subbiah, Vivekanandhan

doi:10.3390/brainsci10120959

Cited by 4 publications

(14 citation statements)

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“…Expression of BAX is only investigated in one study using differentiated SH-SY5Y cells. These results showed increased expression of BAX during and after hypoxia (Sriwastva et al 2020 ). BAX induces cell death via mitochondrial membrane permeabilization.…”

Section: Resultsmentioning

confidence: 89%

“…The consequent mitochondrial membrane depolarization has been found in undifferentiated SH-SY5Y cells (n = 3) (Agudo-Lopez et al 2010 ; Park et al 2017 ; Wang et al 2018b ). Mitochondrial membrane permeabilization by opening of the mitochondrial permeability transition pore and loss of the mitochondrial membrane potential (MMP) has also been established in three studies in undifferentiated and in two studies differentiated SH-SY5Y cells (Lin et al 2020 ; Liu et al 2019a ; Park et al 2017 ; Sriwastva et al 2020 ; Wang et al 2019b ). Normal mitochondrial function was reduced in undifferentiated SH-SY5Y cells after OGD (Herrmann et al 2013 ).…”

Section: Resultsmentioning

confidence: 99%

“…Apoptosis can be triggered through an intrinsic pathway which is regulated by B-cell lymphoma 2 (BCL-2) protein family and is activated by internal signals. The expression of anti-apoptotic BCL-2 has been investigated in 25 studies using undifferentiated SH-SY5Y cells (Chang et al 2017 ; Dong et al 2019 ; Feng et al 2021 ; Gao et al 2020 ; Guo 2019 ; He et al 2014 ; Hu et al 2020 ; Huang et al 2018 ; Li et al 2019b , 2020a ; Liu et al 2018 , 2020 ; Wang et al 2013 , 2019c , 2020b , 2021a , b ; Wu et al 2020a ; Xu et al 2020b ; Yan et al 2020 ; Zhang et al 2016b ; Zhao and Wang 2020 ; Zhi et al 2020 ; Zhou et al 2019 ) and in one study using differentiated SH-SY5Y cells (Sriwastva et al 2020 ). It was found that BCL-2 decreased during and after ischemia/hypoxia.…”

Section: Resultsmentioning

confidence: 99%

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Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

2023

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Translation of neuroprotective treatment effects from experimental animal models to patients with cerebral ischemia has been challenging. Since pathophysiological processes may vary across species, an experimental model to clarify human-specific neuronal pathomechanisms may help. We conducted a scoping review of the literature on human neuronal in vitro models that have been used to study neuronal responses to ischemia or hypoxia, the parts of the pathophysiological cascade that have been investigated in those models, and evidence on effects of interventions. We included 147 studies on four different human neuronal models. The majority of the studies (132/147) was conducted in SH-SY5Y cells, which is a cancerous cell line derived from a single neuroblastoma patient. Of these, 119/132 used undifferentiated SH-SY5Y cells, that lack many neuronal characteristics. Two studies used healthy human induced pluripotent stem cell derived neuronal networks. Most studies used microscopic measures and established hypoxia induced cell death, oxidative stress, or inflammation. Only one study investigated the effect of hypoxia on neuronal network functionality using micro-electrode arrays. Treatment targets included oxidative stress, inflammation, cell death, and neuronal network stimulation. We discuss (dis)advantages of the various model systems and propose future perspectives for research into human neuronal responses to ischemia or hypoxia. Graphical Abstract

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Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

2023

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“…Protein C is a vitamin K-dependent serine protease that is synthesized mainly in the liver and circulates in the plasma. Protein C binds to mEPCR with high affinity, and is converted to activated protein C (APC) by the thrombin–thrombomodulin complex on the surface of endothelial cells through a limited proteolytic process ( 17 ). The mEPCR variant can bind to APC and plays important roles in anticoagulation, anti-inflammatory, cell protection (anti-apoptosis), protecting endothelial barrier function, and promoting neovascularization ( 18 – 22 ).…”

Section: Discussionmentioning

confidence: 99%

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome

Cai

Hao

Chen

et al. 2022

Front. Cardiovasc. Med.

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BackgroundChronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification.MethodsData-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort.ResultsFifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone.ConclusionPlasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.

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“…Protein C is a vitamin Kdependent serine protease that is synthesized mainly in the liver and circulates in the plasma. Protein C binds to mEPCR with high a nity, and is converted to activated protein C (APC) by the thrombinthrombomodulin complex on the surface of endothelial cells through a limited proteolytic process [23]. The mEPCR variant can bind to APC and plays important roles in anticoagulation, anti-in ammatory, cell protection (anti-apoptosis), protecting endothelial barrier function, and promoting neovascularization [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Role of Plasma Proteomics in Predicting the Prognosis of Older Adult Patients with Chronic Coronary Syndrome

Cai¹,

Hao²,

Chen³

et al. 2021

Preprint

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Background: Chronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification.Methods: Data-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay (ELISA) in an independent prospective cohort (n = 352).Results: Fifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. A correlation analysis showed that CETP was positively related to high-density lipoprotein cholesterol and triglyceride, and EPCR was positively related to fibrinogen. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. The cumulative risk duration of patients with high EPCR and CETP levels was significantly shorter than that of patients with low EPCR and CETP levels. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone (AUC 0.732 vs. 0.684, p<0.05).Conclusions: Plasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS. The Framingham CHD risk model combined with EPCR and CETP levels was shown to be a high-performance prognostic model for CCS.

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Neuroprotective Effects of Activated Protein C Involve the PARP/AIF Pathway against Oxygen-Glucose Deprivation in SH-SY5Y Cells

Cited by 4 publications

References 47 publications

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

Neuronal Responses to Ischemia: Scoping Review of Insights from Human-Derived In Vitro Models

Correlation Between Plasma Proteomics and Adverse Outcomes Among Older Men With Chronic Coronary Syndrome

Role of Plasma Proteomics in Predicting the Prognosis of Older Adult Patients with Chronic Coronary Syndrome

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