scholarly journals High doses of vitamin E improve mitochondrial dysfunction in rat hippocampus and frontal cortex upon aging

2011 ◽  
Vol 300 (4) ◽  
pp. R827-R834 ◽  
Author(s):  
Ana Navarro ◽  
Manuel J. Bandez ◽  
Jose M. Lopez-Cepero ◽  
Carmen Gómez ◽  
Alberto Boveris
Keyword(s):  
Vitamin E ◽  
Mitochondrial Dysfunction ◽  
Frontal Cortex ◽  
Mitochondrial Respiration ◽  
Oxidation Products ◽  
Dependent Manner ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Mitochondrial Nitric Oxide Synthase ◽  
High Doses

Rat aging from 4 to 12 mo was accompanied by hippocampus and frontal cortex mitochondrial dysfunction, with decreases of 23 to 53% in tissue and mitochondrial respiration and in the activities of complexes I and IV and of mitochondrial nitric oxide synthase (mtNOS) ( P < 0.02). In aged rats, the two brain areas showed mitochondria with higher content (35–78%) of oxidation products of phospholipids and proteins and with higher (59–95%) rates of O2− and H2O2 production ( P < 0.02). Dietary supplementation with vitamin E (2.0 or 5.0 g/kg of food) from 9 to 12 mo of rat age, restored in a dose-dependent manner, the decreases in tissue and mitochondrial respiration (to 90–96%) and complexes I and IV and mtNOS activities (to 86–88%) of the values of 4-mo-old rats ( P < 0.02). Vitamin E prevented, by 73–80%, the increases in oxidation products, and by 62–68%, the increases in O2− and H2O2 production ( P < 0.05). High resolution histochemistry of cytochrome oxidase in the hippocampal CA1 region showed higher staining in vitamin E-treated rats than in control animals. Aging decreased (19%) hippocampus mitochondrial mass, an effect that was restored by vitamin E. High doses of vitamin E seem to sustain mitochondrial biogenesis in synaptic areas.

scholarly journals The Parkinson’s Disease-Associated Protein DJ-1 Protects Dictyostelium Cells from AMPK-Dependent Outcomes of Oxidative Stress

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1874
Author(s):  
Suwei Chen ◽  
Sarah J. Annesley ◽  
Rasha A. F. Jasim ◽  
Paul R. Fisher
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Cysteine Residue ◽  
Reduced Form ◽  
Dependent Manner ◽  
Loss Of Function ◽  
Cellular Pathology

Mitochondrial dysfunction has been implicated in the pathology of Parkinson’s disease (PD). In Dictyostelium discoideum, strains with mitochondrial dysfunction present consistent, AMPK-dependent phenotypes. This provides an opportunity to investigate if the loss of function of specific PD-associated genes produces cellular pathology by causing mitochondrial dysfunction with AMPK-mediated consequences. DJ-1 is a PD-associated, cytosolic protein with a conserved oxidizable cysteine residue that is important for the protein’s ability to protect cells from the pathological consequences of oxidative stress. Dictyostelium DJ-1 (encoded by the gene deeJ) is located in the cytosol from where it indirectly inhibits mitochondrial respiration and also exerts a positive, nonmitochondrial role in endocytosis (particularly phagocytosis). Its loss in unstressed cells impairs endocytosis and causes correspondingly slower growth, while also stimulating mitochondrial respiration. We report here that oxidative stress in Dictyostelium cells inhibits mitochondrial respiration and impairs phagocytosis in an AMPK-dependent manner. This adds to the separate impairment of phagocytosis caused by DJ-1 knockdown. Oxidative stress also combines with DJ-1 loss in an AMPK-dependent manner to impair or exacerbate defects in phototaxis, morphogenesis and growth. It thereby phenocopies mitochondrial dysfunction. These results support a model in which the oxidized but not the reduced form of DJ-1 inhibits AMPK in the cytosol, thereby protecting cells from the adverse consequences of oxidative stress, mitochondrial dysfunction and the resulting AMPK hyperactivity.

The mitochondrial energy transduction system and the aging process

2007 ◽  
Vol 292 (2) ◽  
pp. C670-C686 ◽  
Author(s):  
Ana Navarro ◽  
Alberto Boveris
Keyword(s):  
Nitric Oxide ◽  
Electron Transfer ◽  
Mitochondrial Dysfunction ◽  
Oxidation Products ◽  
Mitochondrial Content ◽  
Inner Membrane ◽  
Rat Brain And Liver ◽  
Mitochondrial Nitric Oxide Synthase ◽  
Lipid And Protein Oxidation ◽  
Oxide Synthase

Aged mammalian tissues show a decreased capacity to produce ATP by oxidative phosphorylation due to dysfunctional mitochondria. The mitochondrial content of rat brain and liver is not reduced in aging and the impairment of mitochondrial function is due to decreased rates of electron transfer by the selectively diminished activities of complexes I and IV. Inner membrane H+ impermeability and F1-ATP synthase activity are only slightly affected by aging. Dysfunctional mitochondria in aged rodents are characterized, besides decreased electron transfer and O2 uptake, by an increased content of oxidation products of phospholipids, proteins and DNA, a decreased membrane potential, and increased size and fragility. Free radical-mediated oxidations are determining factors of mitochondrial dysfunction and turnover, cell apoptosis, tissue function, and lifespan. Inner membrane enzyme activities, such as those of complexes I and IV and mitochondrial nitric oxide synthase, decrease upon aging and afford aging markers. The activities of these three enzymes in mice brain are linearly correlated with neurological performance, as determined by the tightrope and the T-maze tests. The same enzymatic activities correlated positively with mice survival and negatively with the mitochondrial content of lipid and protein oxidation products. Conditions that increase survival, as vitamin E dietary supplementation, caloric restriction, high spontaneous neurological activity, and moderate physical exercise, ameliorate mitochondrial dysfunction in aged brain and liver. The pleiotropic signaling of mitochondrial H2O2 and nitric oxide diffusion to the cytosol seems modified in aged animals and to contribute to the decreased mitochondrial biogenesis in old animals.

Low, but Not High, Doses of Copper Sulfate Impair Synaptic Plasticity in the Hippocampal CA1 Region In Vivo

2018 ◽  
Vol 185 (1) ◽  
pp. 143-147 ◽  
Author(s):  
Abolfazl Jand ◽  
Mohammad Reza Taheri-nejad ◽  
Masoumeh Mosleh ◽  
Mohammad Reza Palizvan
Keyword(s):  
Synaptic Plasticity ◽  
Copper Sulfate ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
High Doses

scholarly journals P27 Protects Neurons from Ischemic Damage by Suppressing Oxidative Stress and Increasing Autophagy in the Hippocampus

2020 ◽  
Vol 21 (24) ◽  
pp. 9496
Author(s):  
Woosuk Kim ◽  
Hyun Jung Kwon ◽  
Hyo Young Jung ◽  
Kyu Ri Hahn ◽  
Yeo Sung Yoon ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Neuronal Damage ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Membrane Phospholipids ◽  
Ht22 Cells ◽  
H2o2 Treatment ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

p27Kip1 (p27), a well-known cell regulator, is involved in the regulation of cell death and survival. In the present study, we observed the effects of p27 against oxidative stress induced by H2O2 in HT22 cells and transient ischemia in gerbils. Tat (trans-acting activator of transcription) peptide and p27 fusion proteins were prepared to facilitate delivery into cells and across the blood-brain barrier. The tat-p27 fusion protein, rather than its control protein Control-p27, was delivered intracellularly in a concentration and incubation time-dependent manner and showed its activity in HT22 cells. The localization of the delivered Tat-p27 protein was also confirmted in the HT22 cells and hippocampus in gerbils. In addition, the optimal concentration (5 μM) of Tat-p27 was determined to protect neurons from cell death induced by 1 mM H2O2. Treatment with 5 μM Tat-p27 significantly ameliorated H2O2-induced DNA fragmentation and the formation of reactive oxygen species (ROS) in HT22 cells. Tat-p27 significantly mitigated the increase in locomotor activity a day after ischemia and neuronal damage in the hippocampal CA1 region. It also reduced the ischemia-induced membrane phospholipids and ROS formation. In addition, Tat-p27 significantly increased microtubule-associated protein 1A/1B light chain 3A/3B expression and ameliorated the H2O2 or ischemia-induced increases of p62 and decreases of beclin-1 in the HT22 cells and hippocampus. These results suggest that Tat-p27 protects neurons from oxidative or ischemic damage by reducing ROS-induced damage and by facilitating the formation of autophagosomes in hippocampal cells.

scholarly journals Protocatechuic Acid Attenuates Adipogenesis-Induced Inflammation and Mitochondrial Dysfunction in 3T3-L1 Adipocytes via Regulation of AMPK Pathway

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 495-495
Author(s):  
Qiaozhi Zhang ◽  
Elvira Gonzalez de Mejia
Keyword(s):  
Mitochondrial Dysfunction ◽  
Mitochondrial Respiration ◽  
Inflammatory Cytokine ◽  
Protocatechuic Acid ◽  
Cytokine Production ◽  
Dependent Manner ◽  
Inflammatory Cytokine Production ◽  
Anti Inflammatory ◽  
The Impact ◽  
Anti Inflammatory Cytokine

Abstract Objectives To investigate the impact of cyanidin-3-O-glycoside (C3G) and its two major phenolic acid metabolites, protocatechuic acid (PCA) and ferulic acid (FA), on macrophage (MФ) factor-induced inflammation and mitochondrial dysfunction in 3T3-L1 adipocytes. Methods Secretory factors from lipopolysaccharide (LPS)-stimulated RAW 274.7 MФ were used to treat adipocytes to simulate the MФ-adipocyte crosstalk in adipose tissue. Alteration of inflammatory responses, including pro-/anti-inflammatory cytokine production and pro-inflammatory signaling pathway activation were evaluated. Mitochondrial respiration, biogenesis and function in MФ factor-induced adipocytes were investigated and the potential role of C3G, PCA and FA was compared. The AMPK-stimulating actions of PCA were explored via determining its impacts on the phosphorylation pattern of key proteins in the AMPK system. Results In LPS-conditioned media (CM)-treated adipocytes, C3G, PCA and FA suppressed pro-inflammatory cytokine production (TNF-α: −29.0 to −66.2%; IL-6: −6.6 to −38.2%) and enhanced anti-inflammatory cytokine secretion (adiponectin: 16.1–173.3%) in a dose-dependent manner (P &lt; 0.05). C3G, PCA, and FA down-regulated the expression levels of phosphorylated IκBα and JNK in LPS-CM-stressed adipocytes by 50.5–54.5% and 40.3–56.7% (P &lt; 0.05), respectively. C3G, PCA, and FA alleviated MФ factor-triggered oxidative stress via down-regulating mitochondrial superoxide and mitochondrial dysfunction by up-regulating mitochondrial respiration, in terms of adenosine triphosphate production, oxygen consumption and citrate synthase activity. Compared with C3G and FA, PCA showed better capacity in modulating inflammation and mitochondrial dysregulation in LPS-CM-treated adipocytes (P &lt; 0.05). Further, treatment with PCA increased the AMPK, LKB1, CAMKII, p53, and Akt phosphorylation status while decreased activations in the ACC, mTOR, p70S6k and HSL. Conclusions Metabolites of C3G, primarily PCA, alleviated adipogenesis-induced inflammation and mitochondrial alteration in adipocytes, thus having potential implications to prevent adipogenesis-associated disorders. Funding Sources USDA-NIFA-HATCH 1,017,440.

scholarly journals Tat-Endophilin A1 Fusion Protein Protects Neurons from Ischemic Damage in the Gerbil Hippocampus: A Possible Mechanism of Lipid Peroxidation and Neuroinflammation Mitigation as Well as Synaptic Plasticity

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 357
Author(s):  
Hyo Young Jung ◽  
Hyun Jung Kwon ◽  
Woosuk Kim ◽  
In Koo Hwang ◽  
Goang-Min Choi ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Synaptic Plasticity ◽  
Prostaglandin F2α ◽  
Ischemic Damage ◽  
Dependent Manner ◽  
Forebrain Ischemia ◽  
Ht22 Cells ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region

The present study explored the effects of endophilin A1 (SH3GL2) against oxidative damage brought about by H2O2 in HT22 cells and ischemic damage induced upon transient forebrain ischemia in gerbils. Tat-SH3GL2 and its control protein (Control-SH3GL2) were synthesized to deliver it to the cells by penetrating the cell membrane and blood–brain barrier. Tat-SH3GL2, but not Control-SH3GL2, could be delivered into HT22 cells in a concentration- and time-dependent manner and the hippocampus 8 h after treatment in gerbils. Tat-SH3GL2 was stably present in HT22 cells and degraded with time, by 36 h post treatment. Pre-incubation with Tat-SH3GL2, but not Control-SH3GL2, significantly ameliorated H2O2-induced cell death, DNA fragmentation, and reactive oxygen species formation. SH3GL2 immunoreactivity was decreased in the gerbil hippocampal CA1 region with time after ischemia, but it was maintained in the other regions after ischemia. Tat-SH3GL2 treatment in gerbils appreciably improved ischemia-induced hyperactivity 1 day after ischemia and the percentage of NeuN-immunoreactive surviving cells increased 4 days after ischemia. In addition, Tat-SH3GL2 treatment in gerbils alleviated the increase in lipid peroxidation as assessed by the levels of malondialdehyde and 8-iso-prostaglandin F2α and in pro-inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β, and interleukin-6; while the reduction of protein levels in markers for synaptic plasticity, such as postsynaptic density 95, synaptophysin, and synaptosome associated protein 25 after transient forebrain ischemia was also observed. These results suggest that Tat-SH3GL2 protects neurons from oxidative and ischemic damage by reducing lipid peroxidation and inflammation and improving synaptic plasticity after ischemia.

Somatostatin modulates high-voltage-activated Ca2+ channels in freshly dissociated rat hippocampal neurons

1995 ◽  
Vol 74 (3) ◽  
pp. 1028-1036 ◽  
Author(s):  
H. Ishibashi ◽  
N. Akaike
Keyword(s):  
High Voltage ◽  
Hippocampal Neurons ◽  
Pyramidal Neurons ◽  
Low Voltage ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1 ◽  
Ca2 Channels

1. The effects of somatostatin (SS) on the low-voltage-activated and high-voltage-activated (HVA) Ca2+ channels in pyramidal neurons acutely dissociated from the hippocampal CA1 region of 2- to 3-wk-old rats were investigated in a nystatin perforated-patch recording configuration under voltage-clamp conditions. 2. SS had no effect on the low-voltage-activated Ca2+ channel but did inhibit the HVA Ca2+ channel in a concentration-, time-, and voltage-dependent manner. 3. SS showed the activation phase of Ba2+ current (IBa) passing through HVA Ca2+ channels, and the maximum inhibition was 28% of the total current amplitude measured 10 ms after the current activation. The inhibitory effect was eliminated by applying larger depolarizing prepulses. Pretreatment with pertussis toxin (PTX) completely blocked the effect of SS on HVA IBa, suggesting the contribution of PTX-sensitive Gi/Go proteins to the SS-induced inhibition. 4. The applications of forskolin, 8-Br-cAMP, dibutyryl-guanosine 3'5'-cyclic monophosphate, staurosporine, and 1-(5-isoquinolinylsulphonyl)-2-methylpiperazine did not affect either the control HVA IBa or the SS-induced inhibition of HVA IBa. 5. Pretreatment with protein kinase C (PKC) activators had no significant effect on HVA IBa but did remove the inhibition of HVA IBa by SS. 6. Omega-Conotoxin-GVIA, omega-agatoxin-IVA, nicardipine, and omega-conotoxin-MVIIC blocked HVA IBa by 27, 13, 38, and 9% of the total HVA current, respectively, which suggested the existence of N-, P-, L-, and Q-type HVA Ca2+ channels in the hippocampal CA1 pyramidal neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Selective Proteasomal Dysfunction in the Hippocampal CA1 Region after Transient Forebrain Ischemia

2002 ◽  
Vol 22 (6) ◽  
pp. 705-710 ◽  
Author(s):  
Akio Asai ◽  
Nobuyuki Tanahashi ◽  
Jian-hua Qiu ◽  
Nobuhito Saito ◽  
Shunji Chi ◽  
...  
Keyword(s):  
Frontal Cortex ◽  
Neuronal Death ◽  
Proteasome Activity ◽  
26S Proteasome ◽  
Delayed Neuronal Death ◽  
Forebrain Ischemia ◽  
Transient Forebrain Ischemia ◽  
Ca1 Region ◽  
Hippocampal Ca1 Region ◽  
Hippocampal Ca1

Delayed neuronal death in the hippocampal CA1 region after transient forebrain ischemia may share its underlying mechanism with neurodegeneration and other modes of neuronal death. The precise mechanism, however, remains unknown. In the postischemic hippocampus, conjugated ubiquitin accumulates and free ubiquitin is depleted, suggesting impaired proteasome function. The authors measured regional proteasome activity after transient forebrain ischemia in male Mongolian gerbils. At 30 minutes after ischemia, proteasome activity was 40% of normal in the frontal cortex and hippocampus. After 2 hours of reperfusion, it had returned to normal levels in the frontal cortex, CA3 region, and dentate gyrus, but remained low for up to 48 hours in the CA1 region. Thus, the 26S proteasome was globally impaired in the forebrain during transient ischemia and failed to recover only in the CA1 region after reperfusion. The authors also measured 20S and 26S proteasome activities directly after decapitation ischemia (at 5 and 20 minutes) by fractionating the extracts with glycerol gradient centrifugation. Without adenosine triphosphate (ATP), only 20S proteasome activity was detected in extracts from both the hippocampus and frontal cortex. When the extracts were incubated with ATP in an ATP-regenerating system, 26S proteasome activity recovered almost fully in the frontal cortex but only partially in the hippocampus. Thus, after transient forebrain ischemia, ATP-dependent reassociation of the 20S catalytic and PA700 regulatory subunits to form the active 26S proteasome is severely and specifically impaired in the hippocampus. The irreversible loss of proteasome function underlies the delayed neuronal death induced by transient forebrain ischemia in the hippocampal CA1 region.

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