scholarly journals Interactions of aromatase and seladin-1: A neurosteroidogenic and gender perspective

2019 ◽  
Vol 10 (1) ◽  
pp. 264-279 ◽  
Author(s):  
Pelin Kelicen-Ugur ◽  
Mehtap Cincioğlu-Palabıyık ◽  
Hande Çelik ◽  
Hande Karahan
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Neuronal Damage ◽  
Ischemia Reperfusion ◽  
Neuroprotective Activity ◽  
Protective Effects ◽  
Brain Physiology ◽  
Estrogen Synthesis ◽  
Key Enzyme ◽  
And Gender ◽  
The Brain

Abstract Aromatase and seladin-1 are enzymes that have major roles in estrogen synthesis and are important in both brain physiology and pathology. Aromatase is the key enzyme that catalyzes estrogen biosynthesis from androgen precursors and regulates the brain’s neurosteroidogenic activity. Seladin-1 is the enzyme that catalyzes the last step in the biosynthesis of cholesterol, the precursor of all hormones, from desmosterol. Studies indicated that seladin-1 is a downstream mediator of the neuroprotective activity of estrogen. Recently, we also showed that there is an interaction between aromatase and seladin-1 in the brain. Therefore, the expression of local brain aromatase and seladin-1 is important, as they produce neuroactive steroids in the brain for the protection of neuronal damage. Increasing steroid biosynthesis specifically in the central nervous system (CNS) without affecting peripheral hormone levels may be possible by manipulating brain-specific promoters of steroidogenic enzymes. This review emphasizes that local estrogen, rather than plasma estrogen, may be responsible for estrogens’ protective effects in the brain. Therefore, the roles of aromatase and seladin-1 and their interactions in neurodegenerative events such as Alzheimer’s disease (AD), ischemia/reperfusion injury (stroke), and epilepsy are also discussed in this review.

scholarly journals Insulin and α-Tocopherol Enhance the Protective Effect of Each Other on Brain Cortical Neurons under Oxidative Stress Conditions and in Rat Two-Vessel Forebrain Ischemia/Reperfusion Injury

2021 ◽  
Vol 22 (21) ◽  
pp. 11768
Author(s):  
Irina O. Zakharova ◽  
Liubov V. Bayunova ◽  
Inna I. Zorina ◽  
Tatiana V. Sokolova ◽  
Alexander O. Shpakov ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Reperfusion Injury ◽  
Cortical Neurons ◽  
Brain Cortex ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Forebrain Ischemia ◽  
Cultured Cortical Neurons ◽  
The Brain

Clinical trials show that insulin administered intranasally is a promising drug to treat neurodegenerative diseases, but at high doses its use may result in cerebral insulin resistance. Identifying compounds which could enhance the protective effects of insulin, may be helpful to reduce its effective dose. Our aim was thus to study the efficiency of combined use of insulin and α-tocopherol (α-T) to increase the viability of cultured cortical neurons under oxidative stress conditions and to normalize the metabolic disturbances caused by free radical reaction activation in brain cortex of rats with two-vessel forebrain ischemia/reperfusion injury. Immunoblotting, flow cytometry, colorimetric, and fluorometric techniques were used. α-T enhanced the protective and antioxidative effects of insulin on neurons in oxidative stress, their effects were additive. At the late stages of oxidative stress, the combined action of insulin and α-T increased Akt-kinase activity, inactivated GSK-3beta and normalized ERK1/2 activity in cortical neurons, it was more effective than either drug action. In the brain cortex, ischemia/reperfusion increased the lipid peroxidation product content and caused Na+,K+-ATPase oxidative inactivation. Co-administration of insulin (intranasally, 0.25 IU/rat) and α-T (orally, 50 mg/kg) led to a more pronounced normalization of the levels of Schiff bases, conjugated dienes and trienes and Na+,K+-ATPase activity than administration of each drug alone. Thus, α-T enhances the protective effects of insulin on cultured cortical neurons in oxidative stress and in the brain cortex of rats with cerebral ischemia/reperfusion injury.

scholarly journals Thiazoline-related TRPA1 agonist odorants orchestrate survival fate in mice

2020 ◽  
Author(s):  
Tomohiko Matsuo ◽  
Tomoko Isosaka ◽  
Lijun Tang ◽  
Tomoyoshi Soga ◽  
Reiko Kobayakawa ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Cardiopulmonary Arrest ◽  
Ischemia Reperfusion ◽  
Crisis Response ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Immune Functions ◽  
Term Survival ◽  
The Brain ◽  
Innate Fear

SummaryTherapeutic hypothermia protects the brain after cardiopulmonary arrest. Innate fear has evolved to orchestrate protective effects in life-threatening situations. Thus, strong fear perception may induce a specialized life-protective metabolism based on hypothermia/hypometabolism; however, such phenomena and their inducers are yet to be elucidated. Here, we report that thiazoline-related fear odors (tFOs), which are TRPA1 agonists and induce robust innate fear in mice, induced hibernation-like systemic hypothermia/hypometabolism, accelerated glucose uptake in the brain, and suppressed aerobic metabolism via phosphorylation of pyruvate dehydrogenase, thereby enabling long-term survival in a lethal hypoxic environment. In contrast to hibernation, during which immune functions are generally suppressed, tFO-stimulation induced a crisis-response immune state characterized by potentiated innate immune functions but suppressed inflammation with anti-hypoxic ability. Collectively, these responses exerted potent therapeutic effects in cutaneous and cerebral ischemia/reperfusion injury models. Whole brain mapping and chemogenetic activation revealed that sensory representation of tFOs orchestrate survival fate via brain stem Sp5/NST to midbrain PBN pathway. TFO-induced strong crisis perception maximizes latent life-protective effects by shifting metabolism to a crisis response mode characterized by hypothermia, hypometabolism and crisis immunity.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals Kaempferol Ameliorates Oxygen-Glucose Deprivation/Reoxygenation-Induced Neuronal Ferroptosis by Activating Nrf2/SLC7A11/GPX4 Axis

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 923
Author(s):  
Yuan Yuan ◽  
Yanyu Zhai ◽  
Jingjiong Chen ◽  
Xiaofeng Xu ◽  
Hongmei Wang
Keyword(s):  
Lipid Peroxidation ◽  
Cell Death ◽  
Antioxidant Capacity ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Related Factor ◽  
Protective Effects

Kaempferol has been shown to protect cells against cerebral ischemia/reperfusion injury through inhibition of apoptosis. In the present study, we sought to investigate whether ferroptosis is involved in the oxygen-glucose deprivation/reperfusion (OGD/R)-induced neuronal injury and the effects of kaempferol on ferroptosis in OGD/R-treated neurons. Western blot, immunofluorescence, and transmission electron microscopy were used to analyze ferroptosis, whereas cell death was detected using lactate dehydrogenase (LDH) release. We found that OGD/R attenuated SLC7A11 and glutathione peroxidase 4 (GPX4) levels as well as decreased endogenous antioxidants including nicotinamide adenine dinucleotide phosphate (NADPH), glutathione (GSH), and superoxide dismutase (SOD) in neurons. Notably, OGD/R enhanced the accumulation of lipid peroxidation, leading to the induction of ferroptosis in neurons. However, kaempferol activated nuclear factor-E2-related factor 2 (Nrf2)/SLC7A11/GPX4 signaling, augmented antioxidant capacity, and suppressed the accumulation of lipid peroxidation in OGD/R-treated neurons. Furthermore, kaempferol significantly reversed OGD/R-induced ferroptosis. Nevertheless, inhibition of Nrf2 by ML385 blocked the protective effects of kaempferol on antioxidant capacity, lipid peroxidation, and ferroptosis in OGD/R-treated neurons. These results suggest that ferroptosis may be a significant cause of cell death associated with OGD/R. Kaempferol provides protection from OGD/R-induced ferroptosis partly by activating Nrf2/SLC7A11/GPX4 signaling pathway.

scholarly journals The protective effects of pomegranate extracts against renal ischemia-reperfusion injury in male rats

2014 ◽  
Vol 6 (1) ◽  
pp. 46 ◽  
Author(s):  
AhmetA Sancaktutar ◽  
MehmetN Bodakci ◽  
NamıkK Hatipoglu ◽  
Kemal Basarılı ◽  
Haluk Soylemez ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Male Rats ◽  
Protective Effects ◽  
Renal Ischemia Reperfusion Injury

scholarly journals Comparison of the protective effects of desflurane and propofol anesthesia in rats: a hepatic ischemia-reperfusion injury model

2013 ◽  
Vol 43 ◽  
pp. 592-598
Author(s):  
Ayca TAŞ TUNA ◽  
Cengiz Bekir DEMİREL ◽  
Yusuf ÜNAL ◽  
Aslıhan ÇAVUNT BAYRAKTAR ◽  
Demet YILMAZER ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Hepatic Ischemia ◽  
Injury Model ◽  
Hepatic Ischemia Reperfusion

scholarly journals A Hypothesis: Hydrogen Sulfide Might Be Neuroprotective against Subarachnoid Hemorrhage Induced Brain Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Yong-Peng Yu ◽  
Xiang-Lin Chi ◽  
Li-Jun Liu
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion Injury ◽  
Leukocyte Adhesion ◽  
Ischemia Reperfusion ◽  
The Brain

Gases such as nitric oxide (NO) and carbon monoxide (CO) play important roles both in normal physiology and in disease. Recent studies have shown that hydrogen sulfide (H2S) protects neurons against oxidative stress and ischemia-reperfusion injury and attenuates lipopolysaccharides (LPS) induced neuroinflammation in microglia, exhibiting anti-inflammatory and antiapoptotic activities. The gas H2S is emerging as a novel regulator of important physiologic functions such as arterial diameter, blood flow, and leukocyte adhesion. It has been known that multiple factors, including oxidative stress, free radicals, and neuronal nitric oxide synthesis as well as abnormal inflammatory responses, are involved in the mechanism underlying the brain injury after subarachnoid hemorrhage (SAH). Based on the multiple physiologic functions of H2S, we speculate that it might be a promising, effective, and specific therapy for brain injury after SAH.

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