Abstract
Neuronal cell cycle re-entry is pro-apoptotic. The neuroprotective effects and anti-apoptosis of ischemic postconditioning (IPostC) are well established but the underlying mechanism is still unknown. We explored this critical gap in the present study by genomic comparison of ischemic rat cortex following transient middle cerebral artery occlusion (tMCAO) alone and tMCAO+IPostC. The gene expression profiles of ipsilateral cortices were subjected to microarray analysis. RT-PCR, immunoblotting, and immunofluorescence were subsequently used to quantify or localize the cell proliferation marker proliferating cell nuclear antigen (PCNA), positive and negative cell cycle regulators, and related signaling molecules. Microarray analysis revealed that tMCAO-induced transcriptional changes in 40 cell cycle regulators were ameliorated by IPostC, suggesting that IPostC reversed neuronal cell cycle re-entry. IPostC reversed the rise in mRNA levels of positive cell cycle regulators ccnb1, cdk1, cdca2, cdca3, and cdca7. Elevations in cyclin D1 and neuronal cyclin A2 were similarly inhibited as well. tMCAO-induced phosphorylation of extracellular signal-regulated kinase (p-ERK), glycogen synthase kinase-3β (p-GSK-3β), and cAMP response element binding protein (p-CREB) were also all depressed by IPostC. Furthermore, p-ERK colocalized with neuronal cyclin A2. The present study demonstrates the potent inhibitory effect of IPostC treatment on tMCAO-induced cell-cycle reentry and on ERK/CREB and GSK- 3β/CREB signaling. Because neuronal cell cycle re-entry is pro-apoptotic, these findings lend insight into potential mechanisms underlying neuroprotection of IPostC.
Keywords: Brain, cell cycle, genomics, ischemia/reperfusion, postconditioning, extracellular signal-regulated kinase.
CNS & Neurological Disorders - Drug Targets
Title:Ischemic Post-Conditioning Partially Reverses Cell Cycle Reactivity Following Ischemia/Reperfusion Injury: A Genome-Wide Survey
Volume: 12 Issue: 3
Author(s): Haiping Zhao, Yumin Luo, Xiangrong Liu, Rongliang Wang, Feng Yan, Xiaomeng Liu, Sijie Li, Rehana K. Leak and Xunming Ji
Affiliation:
Keywords: Brain, cell cycle, genomics, ischemia/reperfusion, postconditioning, extracellular signal-regulated kinase.
Abstract: Neuronal cell cycle re-entry is pro-apoptotic. The neuroprotective effects and anti-apoptosis of ischemic postconditioning (IPostC) are well established but the underlying mechanism is still unknown. We explored this critical gap in the present study by genomic comparison of ischemic rat cortex following transient middle cerebral artery occlusion (tMCAO) alone and tMCAO+IPostC. The gene expression profiles of ipsilateral cortices were subjected to microarray analysis. RT-PCR, immunoblotting, and immunofluorescence were subsequently used to quantify or localize the cell proliferation marker proliferating cell nuclear antigen (PCNA), positive and negative cell cycle regulators, and related signaling molecules. Microarray analysis revealed that tMCAO-induced transcriptional changes in 40 cell cycle regulators were ameliorated by IPostC, suggesting that IPostC reversed neuronal cell cycle re-entry. IPostC reversed the rise in mRNA levels of positive cell cycle regulators ccnb1, cdk1, cdca2, cdca3, and cdca7. Elevations in cyclin D1 and neuronal cyclin A2 were similarly inhibited as well. tMCAO-induced phosphorylation of extracellular signal-regulated kinase (p-ERK), glycogen synthase kinase-3β (p-GSK-3β), and cAMP response element binding protein (p-CREB) were also all depressed by IPostC. Furthermore, p-ERK colocalized with neuronal cyclin A2. The present study demonstrates the potent inhibitory effect of IPostC treatment on tMCAO-induced cell-cycle reentry and on ERK/CREB and GSK- 3β/CREB signaling. Because neuronal cell cycle re-entry is pro-apoptotic, these findings lend insight into potential mechanisms underlying neuroprotection of IPostC.
Export Options
About this article
Cite this article as:
Zhao Haiping, Luo Yumin, Liu Xiangrong, Wang Rongliang, Yan Feng, Liu Xiaomeng, Li Sijie, Leak Rehana K. and Ji Xunming, Ischemic Post-Conditioning Partially Reverses Cell Cycle Reactivity Following Ischemia/Reperfusion Injury: A Genome-Wide Survey, CNS & Neurological Disorders - Drug Targets 2013; 12 (3) . https://dx.doi.org/10.2174/1871527311312030008
DOI https://dx.doi.org/10.2174/1871527311312030008 |
Print ISSN 1871-5273 |
Publisher Name Bentham Science Publisher |
Online ISSN 1996-3181 |
Call for Papers in Thematic Issues
Diagnosis and treatment of central nervous system infectious diseases
Infectious diseases of the central nervous system (CNS) can be divided into bacterial, tuberculous, viral, fungal, parasitic infections, etc. Early etiological treatment is often the most crucial means to reduce the mortality rate of patients with central nervous system infections, reduce complications and sequelae, and improve prognosis. The initial clinical ...read more
Techniques of Drug Repurposing: Delivering a new life to Herbs & Drugs
Of late, with the adaptation of innovative approaches and integration of advancements made towards medical sciences as well as the availability of a wide range of tools; several therapeutic challenges are being translated into viable clinical solutions, with a high degree of efficacy, safety, and selectivity. With a better understanding ...read more
Trends and perspectives in the rational management of CNS disorders
Central nervous system (CNS) diseases enforce a significant global health burden, driving ongoing efforts to improve our understanding and effectiveness of therapy. This issue investigates current advances in the discipline, focusing on the understanding as well as therapeutic handling of various CNS diseases. The issue covers a variety of diseases, ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Tocopherol and Tocotrienol: Therapeutic Potential in Animal Models of Stress
Current Drug Targets Editorial (Thematic Issue: Biochemical Targets and Biomarkers for Central Nervous System Protection and Monitoring)
CNS & Neurological Disorders - Drug Targets Recent Advances in Characterizing Natural Products that Regulate Autophagy
Anti-Cancer Agents in Medicinal Chemistry The Design and Development of Deferiprone (L1) and Other Iron Chelators for Clinical Use: Targeting Methods and Application Prospects
Current Medicinal Chemistry Vascular and Cardiac Oxidative Stress and Inflammation as Targets for Cardioprotection
Current Pharmaceutical Design Advanced Nanomedicines for the Treatment and Diagnosis of Myocardial Infarction and Heart Failure
Current Drug Targets Diagnostic Criteria for Metabolic Syndrome in Diet-Induced Rodent Models: A Systematic Review
Current Diabetes Reviews Endothelial Progenitor Cells and Vascular Biology in Diabetes Mellitus: Current Knowledge and Future Perspectives
Current Diabetes Reviews <i>Qiliqiangxin</i> Prescription Promotes Angiogenesis of Hypoxic Primary Rat Cardiac Microvascular Endothelial Cells via Regulating miR-21 Signaling
Current Pharmaceutical Design Probenecid: An Emerging Tool for Neuroprotection
CNS & Neurological Disorders - Drug Targets A Key Role for Connexin Hemichannels in Spreading Ischemic Brain Injury
Current Drug Targets Microgravity Alters Cancer Growth and Progression
Current Cancer Drug Targets Editorial on the Occasion of the 20th Anniversary of Endocrine Metabolic Immune Disorders-Drug Targets Journal with a Kaleidoscopic Vision of Selected Publications
Endocrine, Metabolic & Immune Disorders - Drug Targets IL-1 Cytokines in Cardiovascular Disease: Diagnostic, Prognostic and Therapeutic Implications
Cardiovascular & Hematological Agents in Medicinal Chemistry On the Cellular and Molecular Regulatory Transcriptional Mechanisms and Responsive Putative Pathways to Inflammatory Oxidative Stress Revisited: Current Immunological Breakthroughs and Views at a Glance
Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry Dysfunctions of the Diffusional Membrane Pathways Mediated Hemichannels in Inherited and Acquired Human Diseases
Current Vascular Pharmacology Nano-Systems for Advanced Therapeutics and Diagnosis of Atherosclerosis
Current Pharmaceutical Design The Role of Dietary Compounds in the Therapy of Nicotine-Induced Osteoporosis
Current Drug Targets Vasoprotective Actions of the Atrial Natriuretic Peptide
Current Medicinal Chemistry - Cardiovascular & Hematological Agents The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases
Current Pharmaceutical Design