Similar protective effects of BQ-123 and erythropoietin on survival of neural cells and generation of neurons upon hypoxic injury

AbstractSex steroids are known to regulate brain function and their role is so important that several diseases are strictly correlated with the onset of menopause when estrogen-progesterone deficiency makes neural cells much more vulnerable to toxic stimuli. Although in the past years several scientists have focused their studies on in vitro and in vivo effects of sex steroids on the brain, we are still far from complete knowledge. Indeed, contrasting results from large clinical trials have made the entire issue much more complicated. Currently we know that protective effects exerted by sex steroids depend on several factors among which the dose, the health of the cells and the type of molecule being used. In this review, we present an overview of the direct and indirect effects of estrogen and progesterone on the brain with specific focus on the molecular mechanisms by which these molecules act on neural cells.

Download Full-text

Effect of mutation of amino acids 246–251 (KRKHKK) in HSP72 on protein synthesis and recovery from hypoxic injury

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00872.2004 ◽

2005 ◽

Vol 289 (6) ◽

pp. H2519-H2525 ◽

Cited By ~ 9

Author(s):

M. R. Voss ◽

S. Gupta ◽

J. P. Stice ◽

G. Baumgarten ◽

L. Lu ◽

...

Keyword(s):

Protein Synthesis ◽

Dna Synthesis ◽

Nuclear Localization ◽

Nuclear Export ◽

Cell Function ◽

C2c12 Cells ◽

Protective Effects ◽

Nuclear Retention ◽

Hypoxic Injury ◽

Simulated Ischemia

Heat shock protein (HSP)72, the inducible form of HSP70, protects cells against a variety of injuries, but underlying mechanisms are poorly defined. To investigate the protective effects of HSP72, multiple clones expressing wild-type (WT) HSP72 and two mutants with defective nucleolar and nuclear localization (M45 and 985A, respectively) were made with the tet-off system in C2C12 cells. Four different parameters of cell function/injury were examined after simulated ischemia: protein synthesis, polysome formation, DNA synthesis, and lactate dehydrogenase (LDH release). Overexpression of WT HSP72 was also compared to nontransfected C2C12 cells. As expected, overexpression of HSP72 protected against simulated ischemia and reoxygenation for all parameters. In contrast, both M45 and 985A showed abnormal protein synthesis and polysome formation, both after simulated ischemia and under control conditions. Total RNA was slightly reduced in M45 and 985A at baseline, but 1 h after hypoxia, RNA levels were protected in all clones but significantly decreased in nontransfected C2C12 cells. Clones expressing 985A had nuclear retention of mRNA, suggesting that HSP72 is needed for nuclear export of RNA. All clones, both WT and mutant, had protection of DNA synthesis compared to C2C12 cells, but 985A had greater release of LDH after injury than any other group. These results support a multifactoral protective effect of HSP72, some aspects dependent on nuclear localization with stress and some not. The protection of protein synthesis and polysome formation, and abnormalities in these with the mutants, support a role for HSP72 in these processes both in the normal cell and in injury.

Download Full-text

Pseudosterins A–C, Three 1-Ethyl-3-formyl-β-carbolines from Pseudostellaria heterophylla and Their Cardioprotective Effects

Molecules ◽

10.3390/molecules26165045 ◽

2021 ◽

Vol 26 (16) ◽

pp. 5045

Author(s):

Guo-Bo Xu ◽

Qin-Feng Zhu ◽

Zhen Wang ◽

Chun-Li Zhang ◽

Xin Yang ◽

...

Keyword(s):

Quantum Chemical ◽

Functional Food ◽

Previous Investigation ◽

Spectroscopic Analysis ◽

Protective Effects ◽

H9c2 Cells ◽

Hypoxic Injury ◽

Pseudostellaria Heterophylla ◽

Reoxygenation Injury ◽

Cardioprotective Effects

Pseudostellaria heterophylla is used in China not only as a functional food but also as an herb to tonify the spleen, enhance immunity, and treat palpitation. Our previous investigation showed that a fraction enriched in glycosides obtained from the roots of P. heterophylla possessed pronounced protective effects on H9c2 cells against CoCl2-induced hypoxic injury. However, the active compounds responsible for the observed effects were still unknown. In the current investigation, pseudosterins A–C (1–3), three new alkaloids with a 1-ethyl-3-formyl-β-carboline skeleton, together with polydatin, have been isolated from the active fraction. Their structures were elucidated on the basis of spectroscopic analysis and quantum chemical calculations. The four compounds showed cardioprotective effects against sodium hydrosulfite-induced hypoxia-reoxygenation injury in H9c2 cells, with the three alkaloids being more potent. This is also the first report of alkaloids with a β-carboline skeleton isolated from P. heterophylla as cardioprotective agents.

Download Full-text

Thrombopoietin Has Protective Effect in Neonatal Hypoxia-Ischemia Rat Model

Blood ◽

10.1182/blood-2019-131575 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 4898-4898

Author(s):

Liang Li ◽

Liuming Yang ◽

Hongwu Xin ◽

Beng H Chong ◽

Mo Yang

Keyword(s):

Membrane Potential ◽

Protective Effect ◽

Brain Damage ◽

Mitochondrial Membrane Potential ◽

Rat Model ◽

Mitochondrial Membrane ◽

Conflicts Of Interest ◽

Neonatal Rat ◽

Neural Cells ◽

Protective Effects

Thrombopoietin (TPO) is a growth factor for the megakaryocytic lineage. The expression of TPO and TPO receptor (c-mpl) in the central nervous system (CNS) and the role of TPO in neural cells and brain damage models were investigated. Our results showed the expression of TPO in human cerebral hemisphere, cerebellum, cerebrospinal fluid and blood plasma. We found that TPO had a protective effect in hypoxic-ischemic rat model, as indicated by the increased ipsilateral brain weight and neuron density in a neonatal rat model of hypoxic-ischemic brain damage. Recoveries of sensorimotor functions and histopathology were observed in these animals that received TPO. In addition, TPO could promote C17.2 cells proliferation by activating PI3K/Akt signaling pathway, and the proliferation could be reduced to nearly basal level by the pre-treatment with LY 294002. The phosphorylation of AKT, which is a hallmark of activation of each molecule was significantly enhanced after the treatment with TPO in the cells, peaking at 30 min after stimulation with TPO. TPO was also found to have an anti-apoptotic effect which mediated via Bcl-2/BAX and suppressing the mitochondrial membrane potential. Results showed the increased level of Bcl-2 and decreased level of BAX were in the time-dependence manner (0, 5, 15, 30 and 60 mins) in these cells. In addition, the mitochondrial membrane potential was significantly decreased by adding 100 ng/ml TPO. Our results indicated that TPO have neural protective effects. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Protective Effects of Tao-Hong-Si-Wu Decoction on Memory Impairment and Hippocampal Damage in Animal Model of Vascular Dementia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/195835 ◽

2015 ◽

Vol 2015 ◽

pp. 1-12 ◽

Cited By ~ 11

Author(s):

Lan Han ◽

Zhaojie Ji ◽

Weidong Chen ◽

Dengke Yin ◽

Fan Xu ◽

...

Keyword(s):

Vascular Dementia ◽

Memory Impairment ◽

B Cell Lymphoma ◽

Artery Occlusion ◽

Hippocampal Damage ◽

Neural Cells ◽

Protective Effects ◽

Thrombotic Diseases ◽

Endothelial Growth Factor ◽

Cerebral Artery Occlusion

Tao-Hong-Si-Wu decoction (TSD) as a traditional chinese medicine (TCM) has been developed to treat thrombotic diseases for hundreds of years, and vascular dementia (VD) is a cognitive dysfunction syndrome caused by cerebral embolism. In this study, the protective effect of TSD on memory impairment and brain damage in rat model of VD induced by middle cerebral artery occlusion (MCAO) was investigated. The study showed that rats in MCAO treatment with TSD for 14 days significantly improved behavioral function, increased densities of neuron, and induced angiogenesis in the brain compared with model rats. TSD also adjusted the neurotransmitter levels, reduced the content of endothelin-1 (ET-1), and induced the activities of vascular endothelial growth factor (VEGF) in hippocampus. Moreover, the immunohistochemical staining and western blotting results also revealed that TSD decreased apoptosis via upregulated B-cell lymphoma-2 (Bcl-2)/Bcl-2 associated X protein (Bax) ratio. These results demonstrated TSD possesses neuroprotective and antidementia properties by preventing the loss of neural cells, adjusting brain neurotransmitter, promoting cerebral blood circulation, and decreasing apoptosis. These results suggested that TSD might be developed as an effective drug for the prevention of VD.

Download Full-text

Protective Effects of CISD2 and Influence of Curcumin on CISD2 Expression in Aged Animals and Inflammatory Cell Model

Nutrients ◽

10.3390/nu11030700 ◽

2019 ◽

Vol 11 (3) ◽

pp. 700 ◽

Cited By ~ 6

Author(s):

Chai-Ching Lin ◽

Tien-Huang Chiang ◽

Yu-Yo Sun ◽

Muh-Shi Lin

Keyword(s):

Spinal Cord ◽

Mitochondrial Dysfunction ◽

Cell Model ◽

Neural Cells ◽

Protective Effects ◽

Curcumin Treatment ◽

Cord Injury

Background: Inflammation and mitochondrial dysfunction have been linked to trauma, neurodegeneration, and aging. Impairment of CISD2 expression may trigger the aforementioned pathological conditions in neural cells. We previously reported that curcumin attenuates the downregulation of CISD2 in animal models of spinal cord injury and lipopolysaccharide (LPS)-treated neuronal cells. In this study, we investigate (1) the role of CISD2 and (2) how curcumin regulates CISD2 in the aging process. Materials and methods: The serial expression of CISD2 and the efficacy of curcumin treatment were evaluated in old (104 weeks) mice and long-term cultures of neural cells (35 days in vitro, DIV). LPS-challenged neural cells (with or without siCISD2 transfection) were used to verify the role of curcumin on CISD2 underlying mitochondrial dysfunction. Results: In the brain and spinal cord of mice aged P2, 8, 25, and 104 weeks, we observed a significant decrease in CISD2 expression with age. Curcumin treatment in vivo and in vitro was shown to upregulate CISD2 expression; attenuate inflammatory response in neural cells. Moreover, curcumin treatment elevated CISD2 expression levels and prevented mitochondrial dysfunction in LPS-challenged neural cells. The beneficial effects of curcumin in either non-stressed or LPS-challenged cells that underwent siCISD2 transfection were significantly lower than in respective groups of cells that underwent scrambled siRNA-transfection. Conclusions: We hypothesize that the protective effects of curcumin treatment in reducing cellular inflammation associated trauma, degenerative, and aging processes can be partially attributed to elevated CISD2 expression. We observed a reduction in the protective effects of curcumin against injury-induced inflammation and mitochondrial dysfunction in cells where CISD2 expression was reduced by siCISD2.

Download Full-text

Quercetin Improves Cardiomyocyte Vulnerability to Hypoxia by Regulating SIRT1/TMBIM6-Related Mitophagy and Endoplasmic Reticulum Stress

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5529913 ◽

2021 ◽

Vol 2021 ◽

pp. 1-14

Author(s):

Xing Chang ◽

Tian Zhang ◽

Qingyan Meng ◽

ShiyuanWang ◽

Peizheng Yan ◽

...

Keyword(s):

Oxidative Stress ◽

Reactive Oxygen Species ◽

Endoplasmic Reticulum ◽

Cardiovascular Diseases ◽

Endoplasmic Reticulum Stress ◽

Oxygen Species ◽

Protective Effects ◽

Hypoxic Injury ◽

Human Cardiomyocytes ◽

Stress Damage

Cardiomyocyte apoptosis is an important pathological mechanism underlying cardiovascular diseases and is commonly caused by hypoxia. Moreover, hypoxic injury occurs not only in common cardiovascular diseases but also following various treatments of heart-related conditions. One of the major mechanisms underlying hypoxic injury is oxidative stress. Quercetin has been shown to exert antioxidant stress and vascular protective effects, making it a promising candidate for treating cardiovascular diseases. Therefore, we examined the protective effect of quercetin on human cardiomyocytes subjected to hypoxia-induced oxidative stress damage and its underlying mechanism. Human cardiomyocytes were subjected to hypoxia/reoxygenation (H/R) in vitro with or without quercetin pretreatment; thereafter, flow cytometry, Cell Counting Kit-8 assay, laser scanning confocal microscopy, quantitative PCR, western blotting, and enzyme-linked immunosorbent assay were performed to analyze the effects of quercetin on cardiomyocytes. We found that H/R induced reactive oxygen species overproduction and endoplasmic reticulum stress, as well as inhibited the function of the mitochondria/endoplasmic reticulum and mitophagy, eventually leading to apoptosis and decreasing the viability of human cardiomyocytes. Quercetin pretreatment inhibited H/R-mediated overproduction of reactive oxygen species and damage caused by oxidative stress, increased mitophagy, regulated mRNA and protein expression of transmembrane BAX inhibitor-1 motif-containing 6 (TMBIM6), regulated endoplasmic reticulum stress, and improved the vulnerability of human cardiomyocytes to H/R. Furthermore, transfection with short interfering RNA against silent information regulator protein 1 (SIRT1) counteracted the protective effects of quercetin on cardiomyocytes. Thus, quercetin was predicted to regulate mitophagy and endoplasmic reticulum stress through SIRT1/TMBIM6 and inhibit H/R-induced oxidative stress damage. These findings may be useful for developing treatments for hypoxic injury-induced cardiovascular diseases and further highlight the potential of quercetin for regulating mitochondrial quality control and endoplasmic reticulum function.

Download Full-text