scholarly journals Parkia biglobosaImproves Mitochondrial Functioning and Protects against Neurotoxic Agents in Rat Brain Hippocampal Slices

2014 ◽  
Vol 2014 ◽  
pp. 1-15 ◽  
Author(s):  
Kayode Komolafe ◽  
Tolulope M. Olaleye ◽  
Rodrigo L. Seeger ◽  
Fabiano B. Carvalho ◽  
Aline A. Boligon ◽  
...  
Keyword(s):  
Rat Brain ◽  
Neuroprotective Effect ◽  
Hippocampal Slices ◽  
Acetylcholinesterase Activity ◽  
Membrane Lipid ◽  
Ros Generation ◽  
Protective Effects ◽  
Leaf Extracts ◽  
Mitochondrial Ros ◽  
Nonprotein Thiol

Objective. Methanolic leaf extracts ofParkia biglobosa, PBE, and one of its major polyphenolic constituents, catechin, were investigated for their protective effects against neurotoxicity induced by different agents on rat brain hippocampal slices and isolated mitochondria.Methods. Hippocampal slices were preincubated with PBE (25, 50, 100, or 200 µg/mL) or catechin (1, 5, or 10 µg/mL) for 30 min followed by further incubation with 300 µM H2O2, 300 µM SNP, or 200 µM PbCl2for 1 h. Effects of PBE and catechin on SNP- or CaCl2-induced brain mitochondrial ROS formation and mitochondrial membrane potential (ΔΨm) were also determined.Results. PBE and catechin decreased basal ROS generation in slices and blunted the prooxidant effects of neurotoxicants on membrane lipid peroxidation and nonprotein thiol contents. PBE rescued hippocampal cellular viability from SNP damage and caused a significant boost in hippocampus Na+, K+-ATPase activity but with no effect on the acetylcholinesterase activity. Both PBE and catechin also mitigated SNP- or CaCl2-dependent mitochondrial ROS generation. Measurement by safranine fluorescence however showed that the mild depolarization of theΔΨmby PBE was independent of catechin.Conclusion. The results suggest that the neuroprotective effect of PBE is dependent on its constituent antioxidants and mild mitochondrial depolarization propensity.

scholarly journals Angiotensin-(1–7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism

2017 ◽  
Vol 312 (5) ◽  
pp. H980-H991 ◽  
Author(s):  
Lirong Guo ◽  
Ankang Yin ◽  
Qi Zhang ◽  
Tiecheng Zhong ◽  
Stephen T. O’Rourke ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Hypertrophy ◽  
Protective Effect ◽  
Viral Vector ◽  
Ros Generation ◽  
Protective Effects ◽  
Ang Ii ◽  
Mitochondrial Ros ◽  
Dependent Mechanism ◽  
Stimulation Of

The objectives of the present study were to investigate the effect of ANG-(1–7) on the development of cardiac hypertrophy and to identify the intracellular mechanism underlying this action of ANG-(1–7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), ANG II, ANG-(1–7), or ANG II + ANG-(1–7) for 4 wk in normotensive rats. Chronic administration of ANG-(1–7) did not affect either basal blood pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1–7) significantly attenuated ANG II-induced cardiac hypertrophy and perivascular fibrosis in these rats. These effects of ANG-(1–7) were confirmed in cultured cardiomyocytes, in which ANG-(1–7) significantly attenuated ANG II-induced increases in cell size. This protective effect of ANG-(1–7) was significantly attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a mitochondria-targeting superoxide scavenger) as well as blockade of Sirt3 (a deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin (Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment with ANG-(1–7) dramatically increased Sirt3 expression. In addition, ANG-(1–7) attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1–7) increased FoxO3a deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA. In summary, the protective effects of ANG-(1–7) on ANG II-induced cardiac hypertrophy and increased mitochondrial ROS production are mediated by elevated SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in cardiomyocytes. Thus, activation of the ANG-(1–7)/Sirt3 signaling pathway could be a novel therapeutic strategy in the management of cardiac hypertrophy and associated complications. NEW & NOTEWORTHY Chronic subcutaneous ANG-(1–7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1–7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression.

scholarly journals Neuroprotective Action of Human Wharton’s Jelly-Derived Mesenchymal Stromal Cell Transplants in a Rodent Model of Stroke

2018 ◽  
Vol 27 (11) ◽  
pp. 1603-1612 ◽  
Author(s):  
Kuo-Jen Wu ◽  
Seong-Jin Yu ◽  
Chia-Wen Chiang ◽  
Yu-Wei Lee ◽  
B Linju Yen ◽  
...  
Keyword(s):  
Calcium Binding ◽  
Neuroprotective Effect ◽  
Brain Infarction ◽  
Hippocampal Slices ◽  
Wharton’S Jelly ◽  
Trophic Factors ◽  
Neurological Deficits ◽  
Protective Effects ◽  
Wharton's Jelly ◽  
Host Brain

Wharton’s jelly-derived mesenchymal stromal cells (WJ-MSCs) have distinct immunomodulatory and protective effects against kidney, liver, or heart injury. Limited studies have shown that WJ-MSCs attenuates oxygen–glucose deprivation-mediated inflammation in hippocampal slices. The neuroprotective effect of intracerebral WJ-MSC transplantation against stroke has not been well characterized. The purpose of this study was to examine the neuroprotective effect of human WJ-MSC (hWJ-MSC) transplants in an animal model of stroke. Adult male Sprague–Dawley rats were anesthetized and placed in a stereotaxic frame. hWJ-MSCs, pre-labeled with chloromethyl benzamide 1,1’-dioctadecyl-3,3,3’3’- tetramethylindocarbocyanine perchlorate (CM-Dil), were transplanted to the right cerebral cortex at 10 min before a transient (60 min) right middle cerebral artery occlusion (MCAo). Transplantation of hWJ-MSCs significantly reduced neurological deficits at 3 and 5 days after MCAo. hWJ-MSC transplants also significantly reduced brain infarction and microglia activation in the penumbra. Grafted cells carrying CM-Dil fluorescence were identified at the grafted site in the ischemic core; these cells were mostly incorporated into ionized calcium-binding adaptor molecule (+) cells, suggesting these xenograft cells were immuno-rejected by the host. In another set of animals, hWJ-MSCs were transplanted in cyclosporine (CsA)-treated rats. hWJ-MSC transplants significantly reduced brain infarction, improved neurological function, and reduced neuroinflammation. Less phagocytosis of CM-dil-labeled grafted cells was found in the host brain after CsA treatment. Transplantation of hWJ-MSC significantly increased glia cell line-derived neurotrophic factor expression in the host brain. Taken together, our data support that intracerebral transplantation of hWJ-MSCs reduced neurodegeneration and inflammation in the stroke brain. The protective effect did not depend on the survival of grafted cells but may be indirectly mediated through the production of protective trophic factors from the transplants.

scholarly journals Molecular and cellular pathways contributing to brain aging

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Aliabbas Zia ◽  
Ali Mohammad Pourbagher-Shahri ◽  
Tahereh Farkhondeh ◽  
Saeed Samarghandian
Keyword(s):  
Neurodegenerative Diseases ◽  
Neurodegenerative Disorders ◽  
Brain Aging ◽  
Neuroprotective Effect ◽  
Ros Generation ◽  
Brain Health ◽  
Cellular Pathways ◽  
Aging Mechanisms ◽  
Oxidatively Modified ◽  
Biology Of Aging

AbstractAging is the leading risk factor for several age-associated diseases such as neurodegenerative diseases. Understanding the biology of aging mechanisms is essential to the pursuit of brain health. In this regard, brain aging is defined by a gradual decrease in neurophysiological functions, impaired adaptive neuroplasticity, dysregulation of neuronal Ca2+ homeostasis, neuroinflammation, and oxidatively modified molecules and organelles. Numerous pathways lead to brain aging, including increased oxidative stress, inflammation, disturbances in energy metabolism such as deregulated autophagy, mitochondrial dysfunction, and IGF-1, mTOR, ROS, AMPK, SIRTs, and p53 as central modulators of the metabolic control, connecting aging to the pathways, which lead to neurodegenerative disorders. Also, calorie restriction (CR), physical exercise, and mental activities can extend lifespan and increase nervous system resistance to age-associated neurodegenerative diseases. The neuroprotective effect of CR involves increased protection against ROS generation, maintenance of cellular Ca2+ homeostasis, and inhibition of apoptosis. The recent evidence about the modem molecular and cellular methods in neurobiology to brain aging is exhibiting a significant potential in brain cells for adaptation to aging and resistance to neurodegenerative disorders.

scholarly journals Myostatin Deficiency Protects C2C12 Cells from Oxidative Stress by Inhibiting Intrinsic Activation of Apoptosis

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1680
Author(s):  
Marius Drysch ◽  
Sonja Verena Schmidt ◽  
Mustafa Becerikli ◽  
Felix Reinkemeier ◽  
Stephanie Dittfeld ◽  
...  
Keyword(s):  
Intracellular Signaling ◽  
Ischemia Reperfusion ◽  
C2c12 Cell ◽  
C2c12 Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Activity Increase ◽  
Mitogen Activated Protein ◽  
Myostatin Inhibition ◽  
Hypoxia Reoxygenation

Ischemia reperfusion (IR) injury remains an important topic in clinical medicine. While a multitude of prophylactic and therapeutic strategies have been proposed, recent studies have illuminated protective effects of myostatin inhibition. This study aims to elaborate on the intracellular pathways involved in myostatin signaling and to explore key proteins that convey protective effects in IR injury. We used CRISPR/Cas9 gene editing to introduce a Myostatin (Mstn) deletion into a C2C12 cell line. In subsequent experiments, we evaluated overall cell death, activation of apoptotic pathways, ROS generation, lipid peroxidation, intracellular signaling via mitogen-activated protein kinases (MAPKs), cell migration, and cell proliferation under hypoxic conditions followed by reoxygenation to simulate an IR situation in vitro (hypoxia reoxygenation). It was found that mitogen-activated protein kinase kinase 3/6, also known as MAPK/ERK Kinase 3/6 (MEK3/6), and subsequent p38 MAPK activation were blunted in C2C12-Mstn−/− cells in response to hypoxia reoxygenation (HR). Similarly, c-Jun N-terminal kinase (JNK) activation was negated. We also found the intrinsic activation of apoptosis to be more important in comparison with the extrinsic activation. Additionally, intercepting myostatin signaling mitigated apoptosis activation. Ultimately, this research validated protective effects of myostatin inhibition in HR and identified potential mediators worth further investigation. Intercepting myostatin signaling did not inhibit ROS generation overall but mitigated cellular injury. In particular, intrinsic activation of apoptosis origination from mitochondria was alleviated. This was presumably mediated by decreased activation of p38 caused by the diminished kinase activity increase of MEK3/6. Overall, this work provides important insights into HR signaling in C2C12-Mstn−/− cells and could serve as basis for further research.

Long-lasting neuroprotective effect of sildenafil against 3,4-methylenedioxymethamphetamine- induced 5-hydroxytryptamine deficits in the rat brain

2011 ◽  
Vol 90 (2) ◽  
pp. 518-528 ◽  
Author(s):  
Elena Puerta ◽  
Lucia Barros-Miñones ◽  
Isabel Hervias ◽  
Violeta Gomez-Rodriguez ◽  
Lourdes Orejana ◽  
...  
Keyword(s):  
Rat Brain ◽  
Neuroprotective Effect

Protective effects of zinc chelation in traumatic brain injury correlate with upregulation of neuroprotective genes in rat brain

2004 ◽  
Vol 355 (3) ◽  
pp. 221-225 ◽  
Author(s):  
Helen L Hellmich ◽  
Christopher J Frederickson ◽  
Douglas S DeWitt ◽  
Ricardo Saban ◽  
Margaret O Parsley ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Rat Brain ◽  
Protective Effects ◽  
Zinc Chelation

Combined approach to demonstrate acetylcholinesterase activity changes in the rat brain following tabun intoxication and its treatment

2011 ◽  
Vol 22 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Jiri Bajgar ◽  
Petr Hajek ◽  
Jiri Kassa ◽  
Dasa Slizova ◽  
Otakar Krs ◽  
...  
Keyword(s):  
Rat Brain ◽  
Acetylcholinesterase Activity ◽  
Combined Approach
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