Prostate apoptosis response-4 (Par-4) is a ubiquitously expressed pro-apoptotic tumor suppressor protein. Here, we show for the first time, that Par-4 is a novel substrate of caspase-3 during apoptosis. We found that Par-4 is cleaved during cisplatin-induced apoptosis in human normal and cancer cell lines. Par-4 cleavage generates a C-terminal ...

Hyaluronan is a matrix polymer prominent in tissues undergoing rapid growth, development, and repair, in embryology and during malignant progression. It reaches 10(7) Daltons in size but also exists in fragmented forms with size-specific actions. It has intracellular forms whose functions are less well known. Hyaluronan occurs in all vertebrate ...

Acetaminophen (APAP) is hepatotoxic and can cause toxicity in Jurkat T cells. p-Aminophenol (PAP), an industrial chemical and APAP metabolite, is nephrotoxic and hepatotoxic. Its potential toxicity in Jurkat T cells was investigated. PAP (10-250 µM) caused toxicity (decreased survival and increased LDH activity in incubation medium) and GSH depletion. ...

The expression and function of B7-H4, a recently identified co-inhibitory molecule of the B7 superfamily, in the pathogenesis of primary biliary cirrhosis (PBC) is still unclear. Here the expression of B7-H4 in sections from PBC patients (n = 16) was examined by immunohistochemistry and it was detected in primary bile duct epithelial ...

A letter in response to: Yilmaz Y, Kurt R, Kalayci C. Apoptosis in nonalcoholic steatohepatitis with normal aminotransferase values: zooming in on cytokeratin 18 fragments. Biomarkers Med. 4(5), 743-745 (2010).

The peroxisome proliferator-activated receptor (PPAR) δ is involved in tissue repair. In this study, we investigated the functional role of PPARδ in corneal epithelial wound healing. In an in vivo corneal wound-healing model, the changes of PPARδ expression in corneal epithelia were examined by immunofluorescence microscopy, and the effect of ...

Leea indica is a medicinal plant traditionally used to treat cancer. Through bioassay-guided approach, we isolated mollic acid arabinoside (MAA), for the first time from Leea indica. Here, we present the apoptosis-inducing effect of MAA on Ca Ski cervical cancer cells. Based on DAPI staining, MAA-treated cells manifested nuclear shrinkage, ...

Phospholipase D plays an anti-apoptotic role but little is known about dynamics of phospholipase D turnover during apoptosis. We have recently identified phospholipase D1 as a new substrate of caspases which generates the N-terminal and C-terminal fragment of phospholipase D1. In the present study, we tried to investigate whether association ...

Human placental villi are surfaced by a multinucleated and terminally differentiated epithelium, the syncytiotrophoblast, with a subjacent layer of mononucleated cytotrophoblasts that can divide and fuse to replenish the syncytiotrophoblast. The objectives of this study were (i) to develop an approach to definitively identify and distinguish cytotrophoblasts from the syncytiotrophoblast, ...

Objective:  Fractionation of ethyl acetate extract (EA) obtained from Nitraria retusa leaves was assessed using different methods of chromatography, and isorhamnetin3-O-rutinoside (I3-O-R) was isolated from this extract. Its structure was determined using data obtained from (1) H and (13) C NMR spectra, as well as by various correlation experiments (COSY, ...

M-CSF-driven differentiation of peripheral blood monocytes is one of the sources of tissue macrophages. In humans and mice, the differentiation process involves the activation of caspases that cleave a limited number of proteins. One of these proteins is nucleophosmin (NPM1), a multifunctional and ubiquitous protein. Here, we show that caspases ...

The adverse skeletal effects of glucocorticoid excess are due to increased osteoclast survival, decreased production of osteoblasts, and increased apoptosis of osteoblasts and osteocytes, but it remains unknown which of these is the principle cause of the decrease in bone strength. Previous studies suggested that osteocytes contribute to bone strength ...

The characteristics of human asthma are chronic inflammation and airway remodeling. Hyaluronan, a major extracellular matrix component, accumulates during inflammatory lung diseases, including asthma. Hyaluronan fragments stimulate macrophages to produce inflammatory cytokines. We hypothesized that hyaluronan and its receptors would play a role in human asthma. To investigate the role ...

Tree defense against bark beetles (Curculionidae: Scolytinae) and their associated fungi generally comprises some combination of constitutive (primary) and induced (secondary) defenses. In pines, the primary constitutive defense against bark beetles consists of preformed resin stored in resin ducts. Induced defenses at the wound site (point of beetle entry) in ...

Gerodontology 2011; doi: 10.1111/j.1741-2358.2011.00476.x Salivary immunity in elderly individuals presented with Candida-related denture stomatitis Objectives:  Elderly individuals with Candida-related denture stomatitis (DS) present with a reduced defence against Candida albicans. This study evaluated levels of antimicrobial mediators in the elderly DS saliva and salivary neutrophils' activation characteristics compared with elderly ...

Abstract The pubertal mammary gland is an ideal model for experimental morphogenesis. The primary glandular branching morphogenesis occurs at this time, integrating epithelial cell proliferation, differentiation, and apoptosis. Between birth and puberty, the mammary gland exists in a relatively quiescent state. At the onset of puberty, rapid expansion of a ...

Resveratrol, trans-3,5,4'-trihydroxystilbene, is a polyphenolic compound which has been reported to mimic the gene expression patterns seen in whole animals undergoing dietary restriction. The mechanism of action of resveratrol remains poorly understood, but modulation of both cellular proliferation and apoptosis has been proposed as important routes by which the molecule ...

The present study histologically analyzed the salivary glands of Rhipicephalus sanguineus females fed for 2, 4, and 6 days in hosts which had been previously immunized with glandular extracts obtained from females from this same species in different periods of feeding, having as main objective verify the action of these extracts ...

Objective: To evaluate the expression of the apoptotic genes survivin, Bax and Bcl-2 in vasectomized rabbits and to determine their relation with vasectomy-induced spermatogenic impairment and germ cell apoptosis. Materials and Methods: Twelve adult rabbits (6-12 months old) were divided into three groups: sham control, unilateral vasectomy or bilateral vasectomy. ...

Human airways are kept sterile by a mucosal innate defense system that includes mucus secretion. Mucus is secreted in healthy upper airways primarily by submucosal glands and consists of defense molecules mixed with mucins, electrolytes, and water and is also a major component of sputum. Mucus traps pathogens and mechanically ...

Neurofibrillary degeneration and neuronal loss represent key pathological hallmarks of Alzheimer's disease (AD). It has been demonstrated that the decrease of total neuronal numbers correlates with the presence of neurofibrillary degeneration in AD brain. In order to unravel the mechanism leading to the cell death in AD, we developed a ...

Nm23/NDP kinases are multifunctional enzymes involved in the general homeostasis of triphosphate nucleosides. Numerous studies have shown that NDPKs also serve as regulatory factors of various cell activities, not always connected to nucleotide phosphorylation. In particular, the nme-1 gene, encoding the NM23-1/NDPKA protein, has been reported as a metastasis suppressor ...

Osteopontin (OPN) is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family and a cytokine with diverse biologic roles. OPN undergoes extensive post-translational modifications, including polymerization and proteolytic fragmentation, which alters its biologic activity. Recent studies suggest that OPN may contribute to the pathogenesis of asthma. To determine ...

ABSTRACT: In this report the phytochemical profile of Nitraria. Retusa (N. Retusa) leaf extracts were identified and their ability to induce apoptosis in human chronic myelogenous erythroleukaemia (K562) was evaluated. Apoptosis of the human chronic myelogenous erythroleukaemia (K562) was evidenced by investigating DNA fragmentation, PARP cleavage and caspases 3 and ...

Glutamate-induced oxidative stress plays a critical role in the induction of neuronal cell death in a number of disease states. We sought to determine the role of the c-Jun NH(2) -terminal kinase (JNK)-p53-growth arrest and DNA damage-inducible gene (GADD) 45α apoptotic cascade in mediating glutamate-induced oxidative cytotoxicity in hippocampal neuronal ...

Mutations resulting in progranulin haploinsufficiency cause disease in patients with a subset of frontotemporal lobar degeneration; however, the biological functions of progranulin in the brain remain unknown. To address this subject, the present study initially assessed changes in gene expression and cytokine secretion in rat primary cortical neurons treated with ...

Bitter foods are generally recognized as anti-inflammatory agents in traditional Chinese medicine. To verify the anti-inflammatory effects of some bitter compounds in foods or plants, five bitter compounds, aloperine, amygdalin, berberine, crotaline, and naringenin, were selected and added to primary mouse splenocytes in the absence or presence of lipopolysaccharide (LPS) ...

Neurodegenerative diseases trigger neuronal cell death by a variety of endogenous suicide pathways. Although cell death may occur through highly heterogeneous processes, specific cell organelles and stress sensors have shown promise as potential therapeutic targets. The plasma membrane senses stress through residing receptors, which can directly or indirectly activate apoptosis. ...

Increasing evidence suggests that bone marrow derived-mesenchymal stem cells (MSCs) have neuroprotective properties and a major mechanism of action is through their capacity to secrete a diverse range of potentially neurotrophic or anti-oxidant factors. The recent discovery that MSCs secrete superoxide dismutase 3 (SOD3) may help explain studies in which ...

Parkinson's disease (PD) is primarily caused by severe degeneration and loss of dopamine neurons in the substantia nigra pars compacta. Thus, preventing the death of dopaminergic neurons is thought to be a potential strategy to interfere with the development of PD. In the present work, we studied the effect of ...

Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. We have investigated the role of AST in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra (SN) neurons in the mouse model of Parkinson's disease (PD) and 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity of SH-SY5Y human neuroblastoma ...

Abstract A remarkable aspect of adult neurogenesis is that the tight regulation of subventricular zone (SVZ) neuroblast migration is altered after ischemic stroke and newborn neurons emigrate towards the injury. This phenomenon is an essential component of endogenous repair and also serves to illuminate normal mechanisms and rules that govern ...

Glutamate excitotoxicity has been implicated as one of the factors contributing to neuronal apoptosis and is involved in many neurodegenerative diseases. Previous studies suggest that mesenchymal stem cells have the ability to protect cultured neurons from excitotoxicity-induced apoptosis, although the underlying mechanisms are not clear. In this study, we evaluated ...

Glycogen synthase kinase 3 beta (GSK3β) plays a critical role in signal transductions concerning neuronal death. In the present study, we investigated the potential role of GSK3β in 6-hydroxydopamine (6-OHDA)-induced toxicity in human neuroblastoma cell line SH-SY5Y. We assessed the apoptotic proteins and the relative levels of pGSK3β (Ser9) and ...

Over the past two decades it became evident that the immune system plays a central role in modulating learning, memory and neural plasticity. Under normal quiescent conditions, immune mechanisms are activated by environmental/psychological stimuli and positively regulate the remodeling of neural circuits, promoting memory consolidation, hippocampal long-term potentiation (LTP) and ...

Parkinson's disease (PD) is a major age-related neurodegenerative disorder characterized by a massive and specific loss of dopaminergic neurons of the substantia nigra pars compacta. The cellular alterations are clinically translated into an invalidating movement disability associated to three canonical symptoms that are bradykinesia, resting tremor and rigidity. The exact ...

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fibroblast growth factor-inducible 14 (Fn14) are expressed in neurons. Here we demonstrate that TWEAK induces a dose-dependent increase in neuronal death and that this effect is independent of tumor necrosis factor alpha (TNF-α) and mediated by nuclear factor-kappa B ...

Panaxatriol saponins (PTS), the main constituents extracted from Panax notoginseng, a Chinese herbal medicine, has been shown to be an effective agent on various diseases. Our previous study has demonstrated that PTS is an inducer of thioredoxin-1 (Trx-1) and has a possible potential as a therapeutic agent for Parkinson's disease ...

Preconditioning and postconditioning are mild ischemic exposures before or after severe injurious ischemia, respectively, that elicit endogenous neuroprotective responses. Molecular mechanisms of neuroprotection through preconditioning and postconditioning are not completely understood. Here we optimized the in vitro oxygen and glucose deprivation (OGD) models of preconditioning and postconditioning in primary cortical ...

Apoptosis is an important contributing factor during neuronal death in a variety of neurodegenerative disorders, including multiple sclerosis, Parkinson's disease and sciatic nerve injury. Whereas several clinical and preclinical studies have focused on the neuroprotective effects of caspase inhibitors, their clinical benefits are still unclear. Here, we discuss novel alternative ...

Neuronal cell loss underlies the pathological decline in cognition and memory associated with Alzheimer disease (AD). Recently, targeting the endocannabinoid system in AD has emerged as a promising new approach to treatment. Studies have identified neuroprotective roles for endocannabinoids against key pathological events in the AD brain, including cell death ...

Neurogenesis in the adult dentate gyrus (DG) is considered to be partly involved in the action of mood stabilizers. However, it remains unclear how mood stabilizers affect neural precursor cells in adult DG. We have established a culture system of adult rat DG-derived neural precursor cells (ADP) and have shown ...

Recently, the inflammatory and neurodegenerative (I&ND) hypothesis of depression was formulated (Maes et al., 2009), i.e. the neurodegeneration and reduced neurogenesis that characterize depression are caused by inflammation, cell-mediated immune activation and their long-term sequels. The aim of this paper is to review the body of evidence that external stressors ...

In glaucoma, the major cause of global irreversible blindness, there is an urgent need for treatment modalities that directly target the RGCs. The discovery of an alternative therapeutic approach, independent of IOP reduction, is highly sought after, due to the indirect nature and limited effectiveness of IOP lowering therapy in ...

Pathological hallmarks of Parkinson's disease are destruction of dopaminergic neurons in the basal ganglia, especially the substantia nigra, and the presence of Lewy bodies within nerve cells. Environmental toxins are associated with the disease and, in a minority of cases, genetic factors have been identified. Inflammation-with activation of phagocytic microglia, ...

AIM: To investigate the neuroprotective effects of morin on 1-methyl-4-phenylpyridinium ion (MPP(+))-induced apoptosis in neuronal differentiated PC12 cells as well as in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson disease (PD). METHODS: PC12 cells were challenged with MPP(+) in the presence or absence of morin. Cell viability was determined using ...

Applications for noninvasive real-time imaging of apoptosis and neuronal degeneration are hindered by technical limitations in imaging strategies and by existing probes. Monitoring the progression of a cell through apoptosis could provide valuable insight into the temporal events that initiate cell death as well as the potential for rescue of ...

Excitotoxicity is a mechanism of neuronal cell death implicated in a range of neurodegenerative conditions. Systemic administration of the excitotoxin kainic acid (KA) induces inflammation and apoptosis in the hippocampus, resulting in neuronal loss. Evidence indicates that stimulation of glial β(2)-adrenoceptors has anti-inflammatory and neurotrophic properties that could result in ...

Allergic inflammation is the result of a specific pattern of cellular and humoral responses leading to the activation of the innate and adaptive immune system which, in turn, results in physiological and structural changes affecting target tissues such as the airways and the skin. Eosinophils activation and production of soluble ...

The Aconitum has been widely used as an important component in traditional Chinese medicine. However, it can cause neurotoxicity, and the mechanism has not been fully elucidated. The present study aimed to investigate the potential dopaminergic neurotoxicity of Aconitum and its mechanism. We found that Aconitum significantly evoked dopamine release ...