Glycogen synthase kinase-3 (GSK-3) is a pleiotropic serine/threonine protein kinase found in almost all eukaryotes. It is structurally highly conserved and has been identified as a multifaceted enzyme affecting a wide range of biological functions, including gene expression and cellular processes. There are two closely related isoforms of GSK-3; GSK-3α and GSK-3β. The latter appears to play crucial roles in regulating the pathogenesis of diverse diseases, including neurodegenerative disease. The present review focuses on the involvement of this protein in Parkinson's disease (PD), a common neurodegenerative disorder characterized by the gradually progressive and selective loss of dopaminergic neurons, and by intracellular inclusions known as Lewy bodies (LBs) expressed in surviving neurons of the substantia nigra (SN). GSK-3β is involved in multiple signaling pathways and has several phosphorylation targets. Numerous apoptotic conditions can be facilitated by the GSK-3β signaling pathways. Studies have shown that GSK-3β inhibition protects the dopaminergic neurons from various stress-induced injuries, indicating the involvement of GSK-3β in PD pathogenesis. However, the underlying mechanisms of the protective effect of GSK-3β inhibition on dopaminergic neurons in PD is not completely understood. Multiple pathological events have been recognized to be responsible for the loss of dopaminergic neurons in PD, including mitochondrial dysfunction, oxidative stress, protein aggregation and neuroinflammation. The present review stresses the regulatory roles of GSK-3β in these events and in dopaminergic neuron degeneration, in an attempt to gain an improved understanding of the underlying mechanisms and to provide a potential effective therapeutic target for PD.

Reactive oxygen species (ROS) elicited by oxidative stress are widely recognized as a major initiator in the dege-neration of dopaminergic neurons distinctive of Parkinson's disease (PD). The interaction of ROS with mitochondria triggers sequential events in the mitochondrial cell death pathway, which is thought to be responsible for ROS-mediated neurodegeneration in PD. α-lipoic acid (LA) is a pleiotropic compound with potential pharmacotherapeutic value against a range of pathophysiological insults. Its protective actions against oxidative damage by scavenging ROS and reducing production of free radicals have been reported in various in vitro and in vivo systems. This study analyzed the ability of LA to protect PC12 neuronal cells from toxicity of 1-methyl-4-phenylpyridinium (MPP+), the neurotoxic metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which is known to kill dopaminergic neurons selectively and to cause severe parkinsonism-like symptoms in humans and primate animals. Our results demonstrate that the apoptosis of PC12 cells elicited by MPP+ could be significantly prevented by pretreatment with LA for 1 h. In addition, LA inhibits intercellular ROS levels and the mitochondrial transmembrane permeability, the key players in the pathogenesis of PD, thereby protecting dopaminergic neuronal cells against oxidative damage.

Endothelial progenitor cells (EPCs) repair vascular damage and participate in neovascularization. Accumulating evidence has demonstrated that EPCs have therapeutic potential in reactive oxygen species (ROS)-mediated vascular diseases. In this study, to investigate the effects of oxidative stress on EPCs, EPCs were treated with H2O2 at different final concentrations for 3 h. MTT assay, scratch-wound assay and Matrigel invasion assay revealed that cell proliferation, migration and tubule formation and function, respectively, were impaired under H2O2 stress in a concentration-dependent manner. To determine protein response to H2O2 stress, two-dimensional differential in-gel electrophoresis (2D-DIGE) combined with matrix-assisted laser desorption-ionization time-of-flight (MALDI-TOF/TOF) mass spectrometry were performed. The results revealed that triosephosphate isomerase and ADP-sugar pyrophosphatase were downregulated, while peroxiredoxin-2, thioredoxin-dependent peroxide reductase, mitochondrial (Prx‑3), peroxiredoxin-6, EGF-containing fibulin-like extracellular matrix protein 1, vimentin and Rab GDP dissociation inhibitor α were upregulated in the H2O2-treated EPCs. To further confirm the results from mass spectrometry, the expression pattern of Prx-3 in response to H2O2 stress was examined by western blot analysis. The data presented in this study provide novel insight into the defensive mechanisms of EPCs and the pathways of oxidative damage in an oxidative environment.

Endothelial progenitor cells (EPCs) are a cell population mobilized from bone marrow into the peripheral circulation and recruited into sites of vessel injury to participate in blood vessel formation in both physiological and pathological conditions. Due to the lack of unique surface markers and different isolation methods, EPCs represent heterogeneous cell populations including cells of myeloid or endothelial origin. Evidence suggests that EPCs play a critical role in postnatal blood vessel formation and vascular homeostasis and provide a promising therapy for vascular disease. However, the mechanisms by which EPCs participate in new vessel formation are still incompletely understood. We review the process of EPCs in neovascularization including EPC mobilization, migration, adhesion and effect on new vessel formation, in an attempt to better understand the underlying mechanisms and to provide potential effective management for the treatment of patients with vascular disease.

Endothelial Progenitor Cells (EPCs) may play a crucial role in. postnatal vasculogenesis which contribute to the development of vascular biology. So far, there has not a consensus definition of EPCs. In 2004, Ingram developed a single-cell clonogenic assay and identified a unique cell population based on their proliferative potential in. human umbilical cord blood and adult peripheral blood and named this cell population as Endothelial Colony-Forming Cells (ECFCs). Accumulating data suggest that ECFCs possess all the characteristics of EPCs including robust clonal proliferative capacity and the ability to form de novo blood vessels with a lumen in vivo and capillary-like tube in vitro. Therefore, ECFCs may be true EPCs and have been highly concerned as a superior type of cells to treat patients with vascular diseases. This review will focus on the characteristics, hierarchy, expansion, functions of ECFCs. Researchers attempt to provide a comprehensive understanding of the cells to promote the development of cell-based therapy for patients suffering from vascular diseases.

Endothelial progenitor cells (EPCs) which circulate in the peripheral blood and reside in blood vessels are proven to promote the repair of damaged endothelium and improve the function of endothelial cells after vascular injury. Recently, EPCs have been extensively studied as risk biomarkers and a potential therapeutic tool for cardiovascular disease. It is known that oxidative stress is one of the most important pathogenetic factors impairing endothelial function. During the repair process after endothelial injury, EPCs are exposed to oxidative stress. In this study, we treated endothelial colony-forming cells (ECFCs) with hydrogen peroxide (H₂O₂) as an oxidative stress model and observed the changes in cytology and morphology of ECFCs. In addition, we investigated the alterations in oxidative levels of proteins associated with H₂O₂-induced morphological and cytological changes in ECFCs by proteomic analysis of oxidative modification. The results showed that H₂O₂ treatment led to a decreased proliferation, increased apoptosis and impaired tube-forming ability of ECFCs in a dose-dependent manner. Five proteins with upregulated oxidative levels were identified successfully. The upregulated oxidative levels of these five proteins may be responsible for the dysfunction of ECFCs under oxidative stress. Our results may provide some novel insights into the molecular mechanisms of oxidative stress action on ECFCs.