scholarly journals Neuroprotective Effect of Taurine against Cell Death, Glial Changes, and Neuronal Loss in the Cerebellum of Rats Exposed to Chronic-Recurrent Neuroinflammation Induced by LPS

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Samara P. Silva ◽  
Adriana M. Zago ◽  
Fabiano B. Carvalho ◽  
Lucas Germann ◽  
Gabriela de M. Colombo ◽  
...  
Keyword(s):  
Cell Death ◽  
Granular Layer ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
The Face ◽  
Male Wistar Rats ◽  
Cell Layers ◽  
Glial Changes

The present study investigated the neuroprotective effect of taurine against the deleterious effects of chronic-recurrent neuroinflammation induced by LPS in the cerebellum of rats. Adult male Wistar rats were treated with taurine for 28 days. Taurine was administered at a dose of 30 or 100 mg/kg, by gavage. On days 7, 14, 21, and 28, the animals received LPS (250 μg/kg) intraperitoneally. The vehicle used was saline. The animals were divided into six groups: vehicle, taurine 30 mg/kg, taurine 100 mg/kg, LPS, LPS plus taurine 30 mg/kg, and LPS plus taurine 100 mg/kg. On day 29, the animals were euthanized, and the cerebellum was removed and prepared for immunofluorescence analysis using antibodies of GFAP, NeuN, CD11b, and cleaved caspase-3. LPS group showed a reduction in the immunoreactivity of GFAP in the arbor vitae and medullary center and of NeuN in the granular layer of the cerebellar cortex. LPS increased the immunoreactivity of CD11b in the arbor vitae and in the medullary center. Taurine protected against these effects induced by LPS in immunoreactivity of GFAP, NeuN, and CD11b, with the 100 mg/kg dose being the most effective. LPS induced an increase in the number of positive cleaved caspase-3 cells in the Purkinje cell layers, granular layer, arbor vitae, and medullary center. Taurine showed its antiapoptotic activity by reducing the cleaved caspase-3 cells in relation to the LPS group. Here, a potential neuroprotective role of taurine can be seen since this amino acid was effective in protecting the cerebellum of rats against cell death and changes in glial and neuronal cells in the face of chronic-recurrent neuroinflammation.

scholarly journals Cell necrosis and apoptosis are differentially regulated during goitre development and iodine-induced involution

2002 ◽  
Vol 172 (2) ◽  
pp. 375-386 ◽  
Author(s):  
JF Mutaku ◽  
JF Poma ◽  
MC Many ◽  
JF Denef ◽  
MF van Den Hove
Keyword(s):  
Cell Death ◽  
Vitamin E ◽  
Caspase 3 ◽  
Repeated Injection ◽  
Antioxidant Protection ◽  
Cell Necrosis ◽  
Glutathione Peroxidase Activity ◽  
Vitamin E Deficiency ◽  
Male Wistar Rats

Necrosis and apoptosis coexist in the thyroid during goitre development and involution, but little is known about their respective causes. To test the possible role of free radicals, we analysed separately necrosis and apoptosis in male Wistar rats with depressed or normal antioxidant protection. Vitamin E-deficient and -sufficient rats were made goitrous with perchlorate in drinking water; involution was induced by repeated injection of NaI, without or with methimazole. Increase of thyroid malondialdehyde concentration and decrease of glutathione peroxidase activity confirmed the depressed antioxidant protection in vitamin E-deficient rats. Plasma thyroxine and TSH levels were not modified. Necrosis (swollen cells) and apoptosis (pyknotic cells) were quantified on histological sections. In vitamin E-sufficient rats, dead cells were very rare in control thyroids, increased 3-fold in goitre and still further during involution. Necrotic epithelial cells predominated in the goitre and their number declined after iodide supplementation, without or with methimazole. In contrast, the number of apoptotic cells and the caspase-3 activity were increased in goitre and further increased after involution, with two-thirds of pyknotic cells being observed in the interstitium. Apoptosis was prevented by methimazole. Vitamin E deficiency significantly increased total cell death and epithelial cell necrosis and induced the occurrence of much cell debris in the follicular lumen during involution, with no modification of the apoptotic reaction. These results show that the type of cell death is differentially regulated during goitre development and involution: necrosis is related to the oxidative status of the cells, while apoptosis comes with iodine-induced involution.

Abstract WP62: Enhanced Neuroprotection of Normobaric Oxygenation with Ethanol Conferred by Apoptosis Reduction in Acute Ischemic Stroke

Stroke ◽  
2013 ◽  
Vol 44 (suppl_1) ◽  
Author(s):  
Sweena Parmar ◽  
Xiaokun Geng ◽  
Changya Peng ◽  
Murali Guthikonda ◽  
Yuchuan Ding
Keyword(s):  
Cell Death ◽  
Ischemic Stroke ◽  
Acute Ischemic Stroke ◽  
Caspase 3 ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Apoptotic Cell Death ◽  
Ethanol Administration ◽  
Sprague Dawley ◽  
Apoptotic Proteins

Objectives: Normobaric oxygenation (NBO) has been shown to provide neuroprotection in vivo and in vitro . Yet, a recent Phase 2 clinical trial investigating NBO therapy in acute ischemic stroke was terminated due to questionable therapeutic benefit. NBO therapy alone may be insufficient to produce improved outcomes. In our recent study, we demonstrated a strong neuroprotective effect of ethanol at a dose of 1.5 g/kg (equivalent to the human legal driving limit). In this study, we sought to identify whether low-dose ethanol administration enhances the neuroprotection offered by NBO and whether combined administration of NBO with ethanol is associated with reduced apoptosis. Methods: Sprague-Dawley rats were subjected to right middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. Ischemic animals received either an intraperitoneal injection of 1.0 g/kg ethanol, 2 h of 100% NBO, or both ethanol and NBO. The Cell Death Detection ELISA Assay (Roche) was performed to determine apoptotic cell death at 24 h after reperfusion. Levels of pro-apoptotic (Caspase-3, Bcl-2-associated X-BAX, and Apoptosis-Inducing Factor-AIF) and anti-apoptotic proteins (Bcl-2 and Bcl-xL) were determined by Western blot analysis at 3 and 24 h after reperfusion. Results: As expected, untreated ischemic rats had the highest apoptotic cell death. Combined NBO/ethanol therapy decreased cell death by 48%, as compared to 29% with ethanol and 22% with NBO. Similarly, combined NBO/ethanol therapy promoted the greatest expression of anti-apoptotic factors and the lowest expression of pro-apoptotic proteins at 3 h after reperfusion. This effect was maintained at 24 h and even more pronounced for AIF and Caspase-3. Conclusions: Given singularly, NBO and ethanol improved the degree of cell death, decreased the expression of pro-apoptotic proteins, and increased the expression of anti-apoptotic proteins. Yet, when administered together, their effects largely compounded. These results suggest a synergistic neuroprotection offered by NBO with ethanol, which may be attributed at least in part to their shared role in modulating neuronal apoptosis.

scholarly journals Effectiveness of Vitamin C and Vitamin E Antioxidant Combination on Caspase-3 Expression in Wistar White Rat Pulmonum Contusion

2020 ◽  
Vol 3 (1) ◽  
pp. 31-44
Author(s):  
Bermansyah ◽  
Gama Satria ◽  
Ahmad Umar
Keyword(s):  
Cell Death ◽  
Vitamin E ◽  
Vitamin C ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Cell Function ◽  
Pulmonary Contusion ◽  
Tnf Α ◽  
Male Wistar Rats

Introduction.Pulmonary contusions can cause a progressive inflammatory response. Activation of TNF-α cytokines and reactive oxygen species (ROS) can cause pulmonary cell death. Antioxidants can have the potential to neutralize ROS. The purpose of this study is to determine the effectiveness of antioxidant administration in maintaining pulmonary cell function in wistar rats that have been induced to experience pulmonary contusions through caspase-3 levels. Methods.This study was an in vivo experimental study conducted on thirty male wistar rats and divided into five groups (n = 6): control, pulmonary contusion + asthaxanthine 5 mg/kgBW, pulmonary contusion + vitamin C and E 50 mg/kgBW, pulmonary contusion + vitamin C and E 100 mg/kgBW, pulmonary contusion + vitamin C and E 200 mg/kgBW. The value of Caspase-3 is evaluated by the IHC. All data analyzes used SPSS 18. Results. Low doses of antioxidants have the potential to reduce pulmonary cell death in wistar rats induced by pulmonary contusions.Conclussion. Vitamin C and E effective to reduce polmonary cell death in pulmonary contusion.Keywords: antioxidants, vitamin C, vitamin E, pulmonary contusions animal model, apoptosis, caspase-3

Increases in Neutral, Mg2+-Dependent and Acidic, Mg2+-Independent Sphingomyelinase Activities Precede Commitment to Apoptosis and Are Not a Consequence of Caspase 3–Like Activity in Molt-4 Cells in Response to Thymidylate Synthase Inhibition by GW1843

Blood ◽  
1998 ◽  
Vol 91 (11) ◽  
pp. 4350-4360 ◽  
Author(s):  
Ronald M. Laethem ◽  
Yusuf A. Hannun ◽  
Supriya Jayadev ◽  
Connie J. Sexton ◽  
Jay C. Strum ◽  
...  
Keyword(s):  
Cell Death ◽  
T Cell ◽  
Thymidylate Synthase ◽  
Caspase 3 ◽  
Leukemia Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
Ceramide Production

Abstract Thymidylate synthase (TS) inhibition causes cell death, and this enzyme is the target for the important chemotherapy regime 5-fluorouracil/leucovorin. GW1843 (1843U89) is a potent and specific folate analog TS inhibitor in clinical development. Because of the importance of TS as a chemotherapy target, we are studying the mechanism of TS inhibition-induced cell death by GW1843. Ceramide is a regulatory lipid generated by the action of sphingomyelinase and is believed to signal apoptosis. The role of the ceramide in apoptotic signaling was studied in Molt-4 human T-cell leukemia cells undergoing cell death after treatment with GW1843. In response to GW1843, Molt-4 cells undergo apoptosis with both acidic pH, Mg2+-independent sphingomyelinase (ASMase) and neutral pH, Mg2+-dependent sphingomyelinase (NSMase) activities elevated as early steps in the initiation of apoptosis before Molt-4 commitment to death. These activities lead to ceramide production with kinetics consistent with a role as an effector molecule signaling the initiation of apoptosis in Molt-4 cells. These changes were found to be independent of caspase 3–like (CPP32/apopain) activity and DNA degradation, but were not separable from membrane blebbing or cell lysis in this cell line. In this report, kinetic evidence is provided for a role of ceramide in initiating GW1843-induced cell death of Molt-4 T-cell leukemia cells.

Role of caspase-3 in neuronal cell death

1998 ◽  
Vol 5 ◽  
pp. 207
Author(s):  
A. Gorman ◽  
E. Bonfoco ◽  
B. Zhivotovsky ◽  
S. Orrenius ◽  
S. Ceccatelli
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death

2021 ◽  
Author(s):  
Panos Theofilas ◽  
Chao Wang ◽  
David Butler ◽  
Dulce O. Morales ◽  
Cathrine Petersen ◽  
...  
Keyword(s):  
Cell Death ◽  
Cortical Neurons ◽  
Apoptotic Cell ◽  
Neuroprotective Effect ◽  
Neuronal Loss ◽  
Age Related ◽  
Postmortem Brains ◽  
Caspase 6 ◽  
Induced Neurons ◽  
Tau Cleavage

Abstract Background: Tau post-translational modifications (PTMs) are associated with progressive tau accumulation and neuronal loss in tauopathies, including forms of frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Tau proteolysis by caspases, including caspase-6, represents an understudied PTM that may increase neurotoxicity and tau self-aggregation. Methods: To elucidate the presence and temporal course of caspase activation, tau cleavage, and neuronal death, we generated two novel epitope (neoepitope) monoclonal antibodies (mAbs) against caspase-6 tau proteolytic sites. We evaluated tau cleavage and response to apoptotic stress in cortical neurons derived from induced pluripotent stem cells (iPSCs) with frontotemporal dementia (FTD)-causing V337M MAPT mutation. We tested the neuroprotective effect of caspase inhibitors in the induced neurons. We also demonstrated the presence of the tau neoepitopes in postmortem brains from an individual with FTD (V337M MAPT) and an individual with AD, compared to a healthy control.Results: FTLD V337M MAPT and AD postmortem brains showed positivity for both cleaved tau mAbs and active caspase-6. Relative to isogenic wild-type MAPT controls, V337M MAPT neurons cultured for 3 months showed a time-dependent increase in pathogenic tau in the form of caspase-cleaved tau and phosphorylated (p)-tau, and higher levels of tau oligomers. Accumulation of toxic tau species in V337M MAPT neurons was correlated with increased vulnerability to pro-apoptotic stress. Notably, this mutation-associated cell death was pharmacologically rescued by inhibition of effector caspases.Conclusions: Culturing iPSC-derived neurons for three months exposes age-related tau pathologies, including caspase-mediated cleavage, that are also observed in human postmortem brains with abnormal tau deposition. Neoepitope antibodies to caspase-cleaved tau may serve as biomarkers of tau pathology. Furthermore, caspases could be viable therapeutic targets for tau pathogenesis in FTLD and other tauopathies.

Abstract 1950: Role of Superoxide, Nitric Oxide and Peroxynitrite in Doxorubicin-induced Cell Death in vitro and in vivo

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Partha Mukhopadhyay ◽  
Mohanraj Rajesh ◽  
Sandor Bátkai ◽  
György Haskó ◽  
Csaba Szabo ◽  
...  
Keyword(s):  
Cell Death ◽  
Caspase 3 ◽  
Superoxide Generation ◽  
Cytochrome C Release ◽  
Mitochondrial Superoxide ◽  
Induced Apoptosis ◽  
Peroxynitrite Scavengers

Although doxorubicin (DOX) is one of the most potent antitumor agents available, its clinical use is limited because of the risk of severe cardiotoxicity often leading to irreversible congestive heart failure. Apoptotic cell death is a key component in DOX-induced cardiotoxicity, but its trigger(s) and mechanisms are poorly understood. Here, we explore the role of peroxynitrite (a reactive oxidant produced from the diffusion-controlled reaction between nitric oxide and superoxide anion) in DOX-induced cell death. Using a well-established in vivo mouse model of DOX-induced acute heart failure, we demonstrate marked increases in myocardial apoptosis (caspase-3 and 9 gene expression, caspase 3 activity, cytochrome-c release, and TUNEL), iNOS but not eNOS and nNOS expression, 3-nitrotyrosine formation and a decrease in myocardial contractility following DOX treatment. Pre-treatment of mice with peroxynitrite scavengers markedly attenuated DOX-induced myocardial cell death and dysfunction without affecting iNOS expression. DOX induced increased superoxide generation and nitrotyrosine formation in the mitochondria, dissipation of mitochondrial membrane potential, apoptosis (cytochrome-C release, annexin V staining, caspase activation, nuclear fragmentation), and disruption of actin cytoskeleton structure in cardiac-derived H9c2 cells. Selective iNOS inhibitors attenuated DOX-induced apoptosis, without affecting increased mitochondrial superoxide generation, whereas NO donors increased DOX-induced cell death in vitro . The peroxynitrite scavengers FeTMPyP and MnTMPyP markedly reduced both DOX- or peroxynitrite-induced nitrotyrosine formation and cell death in vitro , without affecting DOX-induced increased mitochondrial superoxide formation. Thus, peroxynitrite is a major trigger of DOX-induced apoptosis, and its effective neutralization can be of significant therapeutic benefit.

scholarly journals Role of oxidative stress and caspase 3 in CD47-mediated neuronal cell death

2009 ◽  
Vol 108 (2) ◽  
pp. 430-436 ◽  
Author(s):  
Changhong Xing ◽  
Sunryung Lee ◽  
Woo Jean Kim ◽  
Guang Jin ◽  
Yong-Guang Yang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Caspase 3 ◽  
Neuronal Cell Death ◽  
Neuronal Cell

scholarly journals Intracellular Bax Translocation after Transient Cerebral Ischemia: Implications for a Role of the Mitochondrial Apoptotic Signaling Pathway in Ischemic Neuronal Death

2001 ◽  
Vol 21 (4) ◽  
pp. 321-333 ◽  
Author(s):  
Guodong Cao ◽  
Manabu Minami ◽  
Wei Pei ◽  
Chaohua Yan ◽  
Dexi Chen ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Signaling Pathway ◽  
Mitochondrial Membrane ◽  
Caspase 3 ◽  
Brain Mitochondria ◽  
Caspase 9 ◽  
Bongkrekic Acid

Activation of terminal caspases such as caspase-3 plays an important role in the execution of neuronal cell death after transient cerebral ischemia. Although the precise mechanism by which terminal caspases are activated in ischemic neurons remains elusive, recent studies have postulated that the mitochondrial cell death-signaling pathway may participate in this process. The bcl-2 family member protein Bax is a potent proapoptotic molecule that, on translocation from cytosol to mitochondria, triggers the activation of terminal caspases by increasing mitochondrial membrane permeability and resulting in the release of apoptosis-promoting factors, including cytochrome c. In the present study, the role of intracellular Bax translocation in ischemic brain injury was investigated in a rat model of transient focal ischemia (30 minutes) and reperfusion (1 to 72 hours). Immunochemical studies revealed that transient ischemia induced a rapid translocation of Bax from cytosol to mitochondria in caudate neurons, with a temporal profile and regional distribution coinciding with the mitochondrial release of cytochrome c and caspase-9. Further, in postischemic caudate putamen in vivo and in isolated brain mitochondria in vitro, the authors found enhanced heterodimerization between Bax and the mitochondrial membrane permeabilization-related proteins adenine nucleotide translocator (ANT) and voltage-dependent anion channel. The ANT inhibitor bongkrekic acid prevented Bax and ANT interactions and inhibited Bax-triggered caspase-9 release from isolated brain mitochondria in vitro. Bongkrekic acid also offered significant neuroprotection against ischemia-induced caspase-3 and caspase-9 activation and cell death in the brain. These results strongly suggest that the Bax-mediated mitochondrial apoptotic signaling pathway may play an important role in ischemic neuronal injury.

scholarly journals The neuroprotective effect of nicotine in Parkinson’s disease models is associated with inhibiting PARP-1 and caspase-3 cleavage

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3933 ◽  
Author(s):  
Justin Y.D. Lu ◽  
Ping Su ◽  
James E.M. Barber ◽  
Joanne E. Nash ◽  
Anh D. Le ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Death ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Neuroprotective Effect ◽  
Future Research ◽  
Neuroprotective Effects ◽  
Α7 Nachr ◽  
Parp 1

Clinical evidence points to neuroprotective effects of smoking in Parkinson’s disease (PD), but the molecular mechanisms remain unclear. We investigated the pharmacological pathways involved in these neuroprotective effects, which could provide novel ideas for developing targeted neuroprotective treatments for PD. We used the ETC complex I inhibitor methylpyridinium ion (MPP+) to induce cell death in SH-SY5Y cells as a cellular model for PD and found that nicotine inhibits cell death. Using choline as a nicotinic acetylcholine receptor (nAChR) agonist, we found that nAChR stimulation was sufficient to protect SH-SY5Y cells against cell death from MPP+. Blocking α7 nAChR with methyllycaconitine (MLA) prevented the protective effects of nicotine, demonstrating that these receptors are necessary for the neuroprotective effects of nicotine. The neuroprotective effect of nicotine involves other pathways relevant to PD. Cleaved Poly (ADP-ribose) polymerase-1 (PARP-1) and cleaved caspase-3 were decreased by nicotine in 6-hydroxydopamine (6-OHDA) lesioned mice and in MPP+-treated SH-SY5Y cells. In conclusion, our data indicate that nicotine likely exerts neuroprotective effects in PD through the α7 nAChR and downstream pathways including PARP-1 and caspase-3. This knowledge could be pursued in future research to develop neuroprotective treatments for PD.

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