scholarly journals 17-β Estradiol Rescued Immature Rat Brain against Glutamate-Induced Oxidative Stress and Neurodegeneration via Regulating Nrf2/HO-1 and MAP-Kinase Signaling Pathway

Antioxidants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 892
Author(s):  
Ibrahim Khan ◽  
Kamran Saeed ◽  
Min Gi Jo ◽  
Myeong Ok Kim
Keyword(s):  
Oxidative Stress ◽  
Map Kinase ◽  
Rat Brain ◽  
Biological Activities ◽  
Glutamate Excitotoxicity ◽  
Glutamate Signaling ◽  
Synaptic Markers ◽  
17Β Estradiol ◽  
Brain Oxidative Stress

Dysregulated glutamate signaling, leading to neuronal excitotoxicity and death, has been associated with neurodegenerative pathologies. 17β-estradiol (E2) is a human steroid hormone having a role in reproduction, sexual maturation, brain health and biological activities. The study aimed to explain the neuroprotective role of E2 against glutamate-induced ROS production, MAP kinase-dependent neuroinflammation, synaptic dysfunction and neurodegeneration in the cortex and hippocampus of postnatal day 7 rat brain. Biochemical and immunofluorescence analyses were applied. Our results showed that a single subcutaneous injection of glutamate (10 mg/kg) induced brain oxidative stress after 4 h by disturbing the homeostasis of glutathione (GSH) and revealed an upsurge in ROS and LPO levels and downregulated the expression of Nrf2 and HO-1 antioxidant protein. The glutamate-exposed P7 pups illustrated increased phosphorylation of stress-activated c-Jun N-terminal kinase (JNK) and p38 kinase (p38) and downregulated expression of P-Erk1/2. This was accompanied by pathological neuroinflammation as revealed by enhanced gliosis with upregulated expression of GFAP and Iba-1, and the activation of proinflammatory cytokines (TNF-α) in glutamate-injected P7 pups. Moreover, exogenous glutamate also reduced the expression of synaptic markers (PSD-95, SYP) and induced apoptotic neurodegeneration in the cortical and hippocampal regions by dysregulating the expression of Bax, Bcl-2 and caspase-3 in the developing rat brain. On the contrary, co-treatment of E2 (10 mg/kg) with glutamate significantly abrogated brain neuroinflammation, neurodegeneration and synapse loss by alleviating brain oxidative stress by upregulating the Nrf2/HO-1 antioxidant pathway and by deactivating pro-apoptotic P-JNK/P-p38 and activation of pro-survival P-Erk1/2 MAP kinase pathways. In brief, the data demonstrate the neuroprotective role of E2 against glutamate excitotoxicity-induced neurodegeneration. The study also encourages future studies investigating if E2 may be a potent neuroprotective and neurotherapeutic agent in different neurodegenerative diseases.

Effects of Manganese (Mn) on the Developing Rat Brain: Oxidative-Stress Related Endpoints

2002 ◽  
Vol 23 (2) ◽  
pp. 169-175 ◽  
Author(s):  
Sarah Weber ◽  
David C. Dorman ◽  
Lawrence H. Lash ◽  
Keith Erikson ◽  
Kent E. Vrana ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Rat Brain ◽  
Brain Oxidative Stress ◽  
Developing Rat

Protective Role of Gallic Acid on Sodium Fluoride Induced Oxidative Stress in Rat Brain

2012 ◽  
Vol 89 (1) ◽  
pp. 73-77 ◽  
Author(s):  
Seyed Fazel Nabavi ◽  
Solomon Habtemariam ◽  
Mahtab Jafari ◽  
Antoni Sureda ◽  
Seyed Mohammad Nabavi
Keyword(s):  
Oxidative Stress ◽  
Rat Brain ◽  
Gallic Acid ◽  
Sodium Fluoride ◽  
Protective Role

scholarly journals Insight into Glutamate Excitotoxicity from Synaptic Zinc Homeostasis

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Atsushi Takeda
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Zinc Homeostasis ◽  
Glutamate Excitotoxicity ◽  
Glutamate Signaling ◽  
Synaptic Excitation ◽  
Extracellular Compartment ◽  
Mediating Factor ◽  
Neuron Terminals

Zinc is released from glutamatergic (zincergic) neuron terminals in the hippocampus, followed by the increase in Zn2+concentration in the intracellular (cytosol) compartment, as well as that in the extracellular compartment. The increase in Zn2+concentration in the intracellular compartment during synaptic excitation is mainly due to Zn2+influx through calcium-permeable channels and serves as Zn2+signaling as well as the case in the extracellular compartment. Synaptic Zn2+homeostasis is important for glutamate signaling and altered under numerous pathological processes such as Alzheimer's disease. Synaptic Zn2+homeostasis might be altered in old age, and this alteration might be involved in the pathogenesis and progression of Alzheimer's disease; Zinc may play as a key-mediating factor in the pathophysiology of Alzheimer's disease. This paper summarizes the role of Zn2+signaling in glutamate excitotoxicity, which is involved in Alzheimer's disease, to understand the significance of synaptic Zn2+homeostasis in the pathophysiology of Alzheimer's disease.

Abstract 40: Prothrombotic Role of Platelet Tlr2 in Hyperlipidemia

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Sudipta Biswas ◽  
Liang Xin ◽  
Soumya Panigrahi ◽  
Alejandro Zimman ◽  
Valentin Yakubenko ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Platelet Reactivity ◽  
Biological Activities ◽  
Biologically Active ◽  
Dependent Manner ◽  
Prothrombotic State ◽  
Downstream Signaling ◽  
Subsequent Activation ◽  
Biologically Active Derivatives

A prothrombotic state and increased platelet reactivity are common in hyperlipidemia and oxidative stress. Lipid peroxidation, a major consequence of oxidative stress, generates highly reactive products including hydroxy-w-oxoalkenoic acids that modify autologous proteins generating biologically active derivatives. Phosphatidylethanolamine, the second most abundant eukaryotic phospholipid can also be modified by hydroxy-w-oxoalkenoic acids. However, the conditions leading to accumulation of such derivatives in circulation and their biological activities remain poorly understood. We now show that carboxyalkylpyrrole-phosphatidylethanolamine derivatives (CAP-PE) accumulate in plasma of hyperlipidemic ApoE -/- mice. CAP-PE directly bind to TLR2 and induce platelet integrin alpha 2b beta 3 activation and P-selectin expression in TLR2 dependent manner. Platelet activation by CAP-PE includes assembly of TLR2/TLR1 receptor complex, induction of downstream signaling via MyD88/TIRAP, phosphorylation of IRAK4, and subsequent activation of TRAF6. This in turn activates the Src family kinases, Syk and PLC gamma 2 and platelet integrins. By intravital thrombosis studies we have demonstrated that CAP-PE accelerate thrombosis in TLR2 dependent manner. Furthermore, we demonstrate that TLR2 deficient mice are protected from accelerated thrombosis induced by hyperlipidemia. Taken together, our studies demonstrate a cross-talk between innate immunity and integrin activation signaling pathways in platelets and reveal that TLR2 plays a key role in platelet hyperreactivity and prothrombotic state in hyperlipidemia.

Anxiety-related behavior in hyperhomocysteinemia induced by methionine nutritional overload in rats: role of the brain oxidative stress

2016 ◽  
Vol 94 (10) ◽  
pp. 1074-1082 ◽  
Author(s):  
Dragan Hrncic ◽  
Jelena Mikić ◽  
Aleksandra Rasic-Markovic ◽  
Milica Velimirović ◽  
Tihomir Stojković ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Open Field ◽  
Wistar Rats ◽  
Brain Regions ◽  
Oxidative Status ◽  
Standard Diet ◽  
Male Wistar Rats ◽  
Brain Oxidative Stress ◽  
The Brain

The aim of this study was to examine the effects of a methionine-enriched diet on anxiety-related behavior in rats and to determine the role of the brain oxidative status in these alterations. Adult male Wistar rats were fed from the 30th to 60th postnatal day with standard or methionine-enriched diet (double content comparing with standard diet: 7.7 g/kg). Rats were tested in open field and light–dark tests and afterwards oxidative status in the different brain regions were determined. Hyperhomocysteinemia induced by methionine-enriched diet in this study decreased the number of rearings, as well as the time that these animals spent in the center of the open field, but increased index of thigmotaxy. Oxidative status was selectively altered in the examined regions. Lipid peroxidation was significantly increased in the cortex and nc. caudatus of rats developing hyperhomocysteinemia, but unaltered in the hippocampus and thalamus. Based on the results of this research, it could be concluded that hyperhomocysteinemia induced by methionine nutritional overload increased anxiety-related behavior in rats. These proanxiogenic effects could be, at least in part, a consequence of oxidative stress in the rat brain.

The role of a Brugia malayi p38 MAP kinase ortholog (Bm-MPK1) in parasite anti-oxidative stress responses

2011 ◽  
Vol 176 (2) ◽  
pp. 90-97 ◽  
Author(s):  
Akruti Patel ◽  
Agnieszka Nawrocka Chojnowski ◽  
Katie Gaskill ◽  
William De Martini ◽  
Ronald L. Goldberg ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Map Kinase ◽  
Stress Responses ◽  
Brugia Malayi ◽  
P38 Map Kinase ◽  
Oxidative Stress Responses

scholarly journals 17β-estradiol improves hepatic mitochondrial biogenesis and function through PGC1B

2017 ◽  
Vol 232 (2) ◽  
pp. 297-308 ◽  
Author(s):  
Bel M Galmés-Pascual ◽  
Antonia Nadal-Casellas ◽  
Marco Bauza-Thorbrügge ◽  
Miquel Sbert-Roig ◽  
Francisco J García-Palmer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Biogenesis ◽  
Oxidative Capacity ◽  
Protective Role ◽  
Rat Tissues ◽  
Peroxisome Proliferator ◽  
Ovx Rats ◽  
17Β Estradiol ◽  
And Function

Sexual dimorphism in mitochondrial biogenesis and function has been described in many rat tissues, with females showing larger and more functional mitochondria. The family of the peroxisome proliferator-activated receptor gamma coactivator 1 (PGC1) plays a central role in the regulatory network governing mitochondrial biogenesis and function, but little is known about the different contribution of hepatic PGC1A and PGC1B in these processes. The aim of this study was to elucidate the role of 17β-estradiol (E2) in mitochondrial biogenesis and function in liver and assess the contribution of both hepatic PGC1A and PGC1B as mediators of these effects. In ovariectomized (OVX) rats (half of which were treated with E2) estrogen deficiency led to impaired mitochondrial biogenesis and function, increased oxidative stress, and defective lipid metabolism, but was counteracted by E2 treatment. In HepG2 hepatocytes, the role of E2 in enhancing mitochondrial biogenesis and function was confirmed. These effects were unaffected by the knockdown of PGC1A, but were impaired when PGC1B expression was knocked down by specific siRNA. Our results reveal a widespread protective role of E2 in hepatocytes, which is explained by enhanced mitochondrial content and oxidative capacity, lower hepatic lipid accumulation, and a reduction of oxidative stress. We also suggest a novel hepatic protective role of PGC1B as a modulator of E2 effects on mitochondrial biogenesis and function supporting activation of PGC1B as a therapeutic target for hepatic mitochondrial disorders.

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