Epoxyeicosatrienoic Acid Inhibits the Apoptosis of Cerebral Microvascular Smooth Muscle Cells by Oxygen Glucose Deprivation Via Targeting the JNK/c-Jun and MTOR Signaling Pathways

Overview

Journal Mol Cells

Publisher Elsevier

Specialties Cell Biology
Molecular Biology

Date 2017 Oct 30

PMID 29081082

Citations 6

Authors

Youyang Qu

Yu Liu

Yanmei Zhu

Li Chen

Wei Sun

Yulan Zhu

Affiliations

Soon will be listed here.

Abstract

As a component of the neurovascular unit, cerebral smooth muscle cells (CSMCs) are an important mediator in the development of cerebral vascular diseases such as stroke. Epoxyeicosatrienoic acids (EETs) are the products of arachidonic acid catalyzed by cytochrome P450 epoxygenase. EETs are shown to exert neuroprotective effects. In this article, the role of EET in the growth and apoptosis of CSMCs and the underlying mechanisms under oxygen glucose deprivation (OGD) conditions were addressed. The viability of CMSCs was decreased significantly in the OGD group, while different subtypes of EETs, especially 14,15-EET, could increase the viability of CSMCs under OGD conditions. RAPA (serine/threonine kinase Mammalian Target of Rapamycin), a specific mTOR inhibitor, could elevate the level of oxygen free radicals in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. However, SP600125, a specific JNK (c-Jun N-terminal protein kinase) pathway inhibitor, could attenuate oxygen free radicals levels in CSMCs as well as the anti-apoptotic effects of 14,15-EET under OGD conditions. These results strongly suggest that EETs exert protective functions during the growth and apoptosis of CSMCs, via the JNK/c-Jun and mTOR signaling pathways in vitro. We are the first to disclose the beneficial roles and underlying mechanism of 14,15-EET in CSMC under OGD conditions.

Citing Articles

Epoxyeicosatrienoic Acids Inhibit the Activation of Murine Fibroblasts by Blocking the TGF-1-Smad2/3 Signaling in a PPAR-Dependent Manner.

Tao J, Liu T, Zhang C, Zu C, Yang H, Liu Y Oxid Med Cell Longev. 2022; 2022:7265486.

PMID: 36275905 PMC: 9584742. DOI: 10.1155/2022/7265486.

14,15-Epoxyeicosatrienoic Acid Protect Against Glucose Deprivation and Reperfusion-Induced Cerebral Microvascular Endothelial Cells Injury by Modulating Mitochondrial Autophagy SIRT1/FOXO3a Signaling Pathway and TSPO Protein.

Qu Y, Cao J, Wang D, Wang S, Li Y, Zhu Y Front Cell Neurosci. 2022; 16:888836.

PMID: 35558879 PMC: 9086968. DOI: 10.3389/fncel.2022.888836.

Microglial Activation Is Associated With Vasoprotection in a Rat Model of Inflammatory Retinal Vasoregression.

Riemann S, Kolibabka M, Busch S, Lin J, Hoffmann S, Gretz N Front Physiol. 2021; 12:660164.

PMID: 33981252 PMC: 8107726. DOI: 10.3389/fphys.2021.660164.

Cytochrome P450 Metabolism of Polyunsaturated Fatty Acids and Neurodegeneration.

Sarparast M, Dattmore D, Alan J, Lee K Nutrients. 2020; 12(11).

PMID: 33207662 PMC: 7696575. DOI: 10.3390/nu12113523.

Lipids and Lipid Mediators Associated with the Risk and Pathology of Ischemic Stroke.

Kloska A, Malinowska M, Gabig-Ciminska M, Jakobkiewicz-Banecka J Int J Mol Sci. 2020; 21(10).

PMID: 32443889 PMC: 7279232. DOI: 10.3390/ijms21103618.

References

Sudhahar V, Shaw S, Imig J . Epoxyeicosatrienoic acid analogs and vascular function. Curr Med Chem. 2010; 17(12):1181-90. PMC: 2855336. DOI: 10.2174/092986710790827843. View

Wang H, Lin L, Jiang J, Wang Y, Lu Z, Bradbury J . Up-regulation of endothelial nitric-oxide synthase by endothelium-derived hyperpolarizing factor involves mitogen-activated protein kinase and protein kinase C signaling pathways. J Pharmacol Exp Ther. 2003; 307(2):753-64. DOI: 10.1124/jpet.103.052787. View

Drobny M, Kurca E . Possible extrapyramidal system degradation in Parkinson's disease. Brain Res Bull. 2001; 53(4):425-30. DOI: 10.1016/s0361-9230(00)00367-1. View

Iadecola C . Neurovascular regulation in the normal brain and in Alzheimer's disease. Nat Rev Neurosci. 2004; 5(5):347-60. DOI: 10.1038/nrn1387. View

von Leden R, Yauger Y, Khayrullina G, Byrnes K . Central Nervous System Injury and Nicotinamide Adenine Dinucleotide Phosphate Oxidase: Oxidative Stress and Therapeutic Targets. J Neurotrauma. 2016; 34(4):755-764. PMC: 5335782. DOI: 10.1089/neu.2016.4486. View

Schmidt-Kastner R, Truettner J, Zhao W, Belayev L, Krieger C, Busto R . Differential changes of bax, caspase-3 and p21 mRNA expression after transient focal brain ischemia in the rat. Brain Res Mol Brain Res. 2000; 79(1-2):88-101. DOI: 10.1016/s0169-328x(00)00104-2. View

Iyer A, Brown L . Is mycophenolate more than just an immunosuppressant?--An overview. Indian J Biochem Biophys. 2009; 46(1):25-30. View

Morales Palomares S, Cipolla M . Vascular Protection Following Cerebral Ischemia and Reperfusion. J Neurol Neurophysiol. 2011; 2011. PMC: 3216640. DOI: 10.4172/2155-9562.s1-004. View

Qu Y, Yuan M, Liu Y, Xiao X, Zhu Y . The protective effect of epoxyeicosatrienoic acids on cerebral ischemia/reperfusion injury is associated with PI3K/Akt pathway and ATP-sensitive potassium channels. Neurochem Res. 2014; 40(1):1-14. DOI: 10.1007/s11064-014-1456-2. View

10.

Abbott N, Ronnback L, Hansson E . Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2005; 7(1):41-53. DOI: 10.1038/nrn1824. View

11.

Brooks C, Dong Z . Regulation of mitochondrial morphological dynamics during apoptosis by Bcl-2 family proteins: a key in Bak?. Cell Cycle. 2007; 6(24):3043-7. DOI: 10.4161/cc.6.24.5115. View

12.

Benoit M, Dormond-Meuwly A, Demartines N, Dormond O . Targeting the JNK signaling pathway potentiates the antiproliferative efficacy of rapamycin in LS174T colon cancer cells. J Surg Res. 2011; 167(2):e193-8. DOI: 10.1016/j.jss.2011.01.015. View

13.

Sawada M, Nakashima S, Banno Y, Yamakawa H, Takenaka K, Shinoda J . Influence of Bax or Bcl-2 overexpression on the ceramide-dependent apoptotic pathway in glioma cells. Oncogene. 2000; 19(31):3508-20. DOI: 10.1038/sj.onc.1203699. View

14.

Okuno S, Saito A, Hayashi T, Chan P . The c-Jun N-terminal protein kinase signaling pathway mediates Bax activation and subsequent neuronal apoptosis through interaction with Bim after transient focal cerebral ischemia. J Neurosci. 2004; 24(36):7879-87. PMC: 6729938. DOI: 10.1523/JNEUROSCI.1745-04.2004. View

15.

Tong H, Chen W, Steenbergen C, Murphy E . Ischemic preconditioning activates phosphatidylinositol-3-kinase upstream of protein kinase C. Circ Res. 2000; 87(4):309-15. DOI: 10.1161/01.res.87.4.309. View

16.

Imig J . Targeting epoxides for organ damage in hypertension. J Cardiovasc Pharmacol. 2010; 56(4):329-35. PMC: 3071608. DOI: 10.1097/FJC.0b013e3181e96e0c. View

17.

Lee R . Morphology of cerebral arteries. Pharmacol Ther. 1995; 66(1):149-73. DOI: 10.1016/0163-7258(94)00071-a. View

18.

Koehler R, Roman R, Harder D . Astrocytes and the regulation of cerebral blood flow. Trends Neurosci. 2009; 32(3):160-9. DOI: 10.1016/j.tins.2008.11.005. View

19.

Medhora M, Narayanan J, Harder D . Dual regulation of the cerebral microvasculature by epoxyeicosatrienoic acids. Trends Cardiovasc Med. 2001; 11(1):38-42. DOI: 10.1016/s1050-1738(01)00082-2. View

20.

Charriaut-Marlangue C . Apoptosis: a target for neuroprotection. Therapie. 2004; 59(2):185-90. DOI: 10.2515/therapie:2004035. View