scholarly journals Differential effects of GH and GH-releasing peptide-6 on astrocytes

2013 ◽  
Vol 218 (3) ◽  
pp. 263-274 ◽  
Author(s):  
Eva Baquedano ◽  
Julie A Chowen ◽  
Jesús Argente ◽  
Laura M Frago
Keyword(s):  
Wistar Rats ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
Astrocytoma Cells ◽  
Proliferation And Differentiation ◽  
C6 Astrocytoma ◽  
Male Wistar Rats ◽  
Independent Effects ◽  
Stimulation Of

GH and GH secretagogues (GHSs) are involved in many cellular activities such as stimulation of mitosis, proliferation and differentiation. As astrocytes are involved in developmental and protective functions, our aim was to analyse the effects of GH and GH-releasing hexapeptide on astrocyte proliferation and differentiation in the hypothalamus and hippocampus. Treatment of adult male Wistar rats with GH (i.v., 100 μg/day) for 1 week increased the levels of glial fibrillary acidic protein (GFAP) and decreased the levels of vimentin in the hypothalamus and hippocampus. These changes were not accompanied by increased proliferation. By contrast, GH-releasing hexapeptide (i.v., 150 μg/day) did not affect GFAP levels but increased proliferation in the areas studied. To further study the intracellular mechanisms involved in these effects, we treated C6 astrocytoma cells with GH or GH-releasing hexapeptide and the phosphatidylinositol 3′-kinase (PI3K) inhibitor, LY294002, and observed that the presence of this inhibitor reverted the increase in GFAP levels induced by GH and the proliferation induced by GH-releasing hexapeptide. We conclude that although GH-releasing hexapeptide is a GHS, it may exert GH-independent effects centrally on astrocytes when administered i.v., although the effects of both substances appear to be mediated by the PI3K/Akt pathway.

scholarly journals GABA and glycine receptors in the nucleus ambiguus mediate tachycardia elicited by chemical stimulation of the hypothalamic arcuate nucleus

2015 ◽  
Vol 309 (1) ◽  
pp. H174-H184 ◽  
Author(s):  
Vineet C. Chitravanshi ◽  
Kazumi Kawabe ◽  
Hreday N. Sapru
Keyword(s):  
Paraventricular Nucleus ◽  
Wistar Rats ◽  
Arcuate Nucleus ◽  
Chemical Stimulation ◽  
Nucleus Ambiguus ◽  
Glycine Receptors ◽  
Inhibitory Neurotransmitters ◽  
Hypothalamic Arcuate Nucleus ◽  
Male Wistar Rats ◽  
Stimulation Of

We have previously reported that stimulation of the hypothalamic arcuate nucleus (ARCN) by microinjections of N-methyl-d-aspartic acid (NMDA) elicits tachycardia, which is partially mediated via inhibition of vagal inputs to the heart. The neuronal pools and neurotransmitters in them mediating tachycardia elicited from the ARCN have not been identified. We tested the hypothesis that the tachycardia elicited from the ARCN may be mediated by inhibitory neurotransmitters in the nucleus ambiguus (nAmb). Experiments were done in urethane-anesthetized, artificially ventilated, male Wistar rats. In separate groups of rats, unilateral and bilateral microinjections of muscimol (1 mM), gabazine (0.01 mM), and strychnine (0.5 mM) into the nAmb significantly attenuated tachycardia elicited by unilateral microinjections of NMDA (10 mM) into the ARCN. Histological examination of the brains showed that the microinjections sites were within the targeted nuclei. Retrograde anatomic tracing from the nAmb revealed direct bilateral projections from the ARCN and hypothalamic paraventricular nucleus to the nAmb. The results of the present study suggest that tachycardia elicited by stimulation of the ARCN by microinjections of NMDA is mediated via GABAA and glycine receptors located in the nAmb.

scholarly journals Tackling of Renal Carcinogenesis in Wistar Rats by Silybum marianum Total Extract, Silymarin, and Silibinin via Modulation of Oxidative Stress, Apoptosis, Nrf2, PPARγ, NF-κB, and PI3K/Akt Signaling Pathways

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Nour Y. S. Yassin ◽  
Sameh F. AbouZid ◽  
Asmaa M. El-Kalaawy ◽  
Tarek M. Ali ◽  
Basem H. Elesawy ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Wistar Rats ◽  
Caspase 3 ◽  
Akt Pathway ◽  
Molecular Pathways ◽  
Silybum Marianum ◽  
Total Extract ◽  
Renal Carcinogenesis ◽  
Proinflammatory Mediators ◽  
Male Wistar Rats

The present work was designed to assess the efficacy of Silybum marianum total extract (STE), silymarin (Sm), and silibinin (Sb) against experimentally induced renal carcinogenesis in male Wistar rats and their roles in regulating oxidative stress, inflammation, apoptosis, and carcinogenesis. The diethylnitrosamine (DEN)/2-acetylaminofluorene (AAF)/carbon tetrachloride (CCl4)-administered rats were orally treated with STE (200 mg/kg b.w.), Sm (150 mg/kg b.w.), and Sb (5 mg/kg b.w.) every other day either from the 1st week or from the 16th week of carcinogen administration to the end of 25th week. The treatments with STE, Sm, and Sb attenuated markers of toxicity in serum, decreased kidney lipid peroxidation (LPO), and significantly reinforced the renal antioxidant armory. The biochemical results were further confirmed by the histopathological alterations. The treatments also led to suppression of proinflammatory mediators such as NF-κβ, p65, Iκβα, and IL-6 in association with inhibition of the PI3K/Akt pathway. Furthermore, they activated the expressions of PPARs, Nrf2, and IL-4 in addition to downregulation of apoptotic proteins p53 and caspase-3 and upregulation of antiapoptotic mediator Bcl-2. The obtained data supply potent proof for the efficacy of STE, Sm, and Sb to counteract renal carcinogenesis via alteration of varied molecular pathways.

Differential Effects of Three Small Molecules Blocking Phosphatidylinositol-3 Kinase or AKT in Hodgkin Disease Cell Lines: Induction of Apoptosis and Cell Cycle Arrest.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 428-428 ◽  
Author(s):  
Georgios V. Georgakis ◽  
Yang Li ◽  
Georgios Z. Rassidakis ◽  
Jeffrey L. Medeiros ◽  
Gordon B. Mills ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Small Molecules ◽  
Cell Cycle Arrest ◽  
Cell Lines ◽  
Hodgkin Disease ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
Cycle Arrest ◽  
Induction Of Apoptosis

Abstract Several types of tumor cells utilize the phosphatidylinositol 3 Kinase (PI3K)/AKT pathway to support their growth and survival, and blockade of this pathway has been shown to have an antiproliferative effect in these cells. The significance of this survival pathway in Hodgkin disease (HD), and in particular, the neoplastic Hodgkin and Reed-Sternberg (H/RS) of Hodgkin disease (HD) is unknown. We studied routinely processed tissue sections of 42 cases of primary HD (n=42, 35 classical HD and 7 nodular lymphocyte predominant) for the expression of the active phosphorylated form of AKT. We also studied AKT expression in a panel of 4 well-characterized HD-derived cell lines (HD-MyZ, HD-LM2, L-428, and KM-H2). 27 of 42 (64.3%) cases of primary HD sections expressed phospho AKT (23/35 classical and 4/7 nodular lymphocyte predominant). Cultured H/RS cells also showed constitutive phosphorylation of AKT on Ser473. CD30 ligand (CD30L), CD40L and RANKL, increased the phosphorylation of AKT and downstream molecules as early as 1 hour. The effect of 3 small molecule inhibitors of PI3K/AKT pathway (PI3K inhibitor LY294002; AKT inhibitors QLT0394 and QLT0395 from QLT Inc, Vancouver, Canada) on cell proliferation and survival of cultured H/RS cells was examined by the MTS assay. The PI3K inhibitor LY294002 showed antiproliferative activity in a time and dose dependent manner in all cell lines tested. This antiproliferative effect was primarily due to cell cycle arrest in G0/G1 phase, as determined by propidium iodide staining, and to a less extent due to induction of apoptosis, as determined by the Annexin-V binding assay. However, when the AKT inhibitors QLT0394 and QLT0395 were used, they primarily induced apoptosis even at nanomolar doses. Apoptosis was mediated by caspase 8 activation as determined by western blot and was partially reversed by the pancaspase inhibitor ZVAD-FMK. Both AKT inhibitors alteredf AKT phosphorylation within 24 hours, and reduced phosphorylation of downstream molecules, such as 4E-BP1. Moreover, the AKT inhibitor QLT0395 showed downregulation of MDM2 and cyclin D1 within 24 hours, and increased ERK1/2 phosphorylation with subsequent decrease of total ERK1/2 levels at the same time frame, but had no effect in BCL-2, cFLIP or Bax. Importantly, both AKT inhibitors (QLT0394 and QLT0395) maintained their killing activity even in the presene of CD30L, CD40L, and RANKL. These preclinical data suggest that small molecules hitting different targets within PI3K/AKT pathway may have different effects on proliferation and apoptosis and that blockade of this pathway may be of therapeutic value in the treatment of patients with HD.

GABAergic effects on the depressor responses elicited by stimulation of central nucleus of the amygdala

1999 ◽  
Vol 276 (1) ◽  
pp. H242-H247 ◽  
Author(s):  
John Ciriello ◽  
Stefanie Roder
Keyword(s):  
Arterial Pressure ◽  
Receptor Antagonist ◽  
Wistar Rats ◽  
Cardiovascular Responses ◽  
Systemic Arterial Pressure ◽  
The Other ◽  
Central Nucleus ◽  
Male Wistar Rats ◽  
The Mean ◽  
Stimulation Of

GABAergic inputs have been demonstrated in the central nucleus of the amygdala (ACe). However, the contribution of these inhibitory inputs to the cardiovascular responses elicited from the ACe is not known. Experiments were done in chloralose-anesthetized, paralyzed, and artificially ventilated male Wistar rats to investigate the effects of microinjections of GABA, the selective GABAA-receptor antagonist bicuculline, or the GABAB-receptor antagonist phaclofen, in the ACe on the mean arterial pressure (MAP) and heart rate (HR) responses elicited byl-glutamate (Glu) stimulation of the ACe. Microinjections of Glu in the ACe elicited decreases in MAP (−13.7 ± 1.6 mmHg) and HR (−5.3 ± 1.9 beats/min). The MAP and HR responses elicited by Glu stimulation of the ACe were significantly reduced (89%) by the prior microinjection of GABA in the same ACe site. In addition, at some sites in the ACe at which microinjection of Glu did not elicit depressor responses, Glu injections in the presence of phaclofen elicited decreases in MAP (−9.5 ± 1.0 mmHg) and variable changes in HR. On the other hand, the magnitude of the depressor responses elicited during stimulation of the ACe site in the presence of bicuculline was significantly attenuated (60%), whereas phaclofen had no effect on the magnitude of the depressor responses elicited by Glu stimulation of the ACe. These data suggest that GABAergic mechanisms in the ACe alter the excitability of ACe neurons involved in mediating changes in systemic arterial pressure and HR.

scholarly journals Continuous Electrical Current and Zinc Sulphate Administered by Transdermal Iontophoresis Improves Skin Healing in Diabetic Rats Induced by Alloxan: Morphological and Ultrastructural Analysis

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Lucas Langoni Cassettari ◽  
Pedro Colli Rocha Dias ◽  
Amanda Natália Lucchesi ◽  
Maurício Ferraz de Arruda ◽  
Érika Veruska Paiva Ortolan ◽  
...  
Keyword(s):  
Wistar Rats ◽  
Breaking Strength ◽  
Electrical Current ◽  
Diabetic Rats ◽  
Ultrastructural Changes ◽  
Surgical Wounds ◽  
Male Wistar Rats ◽  
Transdermal Iontophoresis ◽  
Skin Healing ◽  
Stimulation Of

Purpose.Evaluated the effects of continuous electrical current (CEC) or zinc administrated by transdermal iontophoresis (Zn+TDI).Methods.120 male Wistar rats were submitted to an incision surgery at the anterior region of abdomen and distributed into 6 experimental groups with 40 animals: 3 diabetic groups and 3 normal groups, untreated and treated with CEC alone or with Zn + TDI. Each group was further divided into 4 subgroups with 10 rats each to be evaluated on the 4th, 7th, 14th, and 21st day after surgery. In each period, clinical and laboratory parameters from the animals were analyzed.Results. The analysis by optical and scanning electron microscopy showed a delay in the phases of wound healing in diabetic rats without treatment in all periods of the experiment; breaking strength (BS) was significantly reduced in skin scars of untreated diabetic rats when compared to other groups. In contrast, BS in skin scars of nondiabetic groups and diabetic rats treated with Zn + TDI showed significant increase in those, besides not presenting delayed healing.Conclusion. Electrical stimulation of surgical wounds used alone or in association with zinc by TDI is able to consistently improve the morphological and ultrastructural changes observed in the healing of diabetic animals.

scholarly journals Interaction of Sodium Valproate With Low-Frequency Electrical Stimulation During Kindlingn

2020 ◽  
Vol 11 (6) ◽  
pp. 831-840
Author(s):  
Raha Zalkhani ◽  
◽  
Ahmad Ali Moazedi ◽  
Zohreh Ghotbeddin ◽  
Mahdi Pourmahdi Borujeni ◽  
...  
Keyword(s):  
Electrical Stimulation ◽  
Sodium Valproate ◽  
Wistar Rats ◽  
Critical Role ◽  
Low Frequency ◽  
Epileptic Activity ◽  
Fourth Stage ◽  
Maximum Duration ◽  
Male Wistar Rats ◽  
Stimulation Of

Introduction: The interaction between antiepileptic drugs and brain electrical stimulation is a potential therapy to control seizures in patients with pharmacoresistance to drugs. So, the present study aimed to design to determine the effect of a subeffective dose of sodium valproate combined with low-frequency electrical stimulation during kindling. Methods: One tripolar electrode was implanted stereotactically in the CA1 hippocampus of male Wistar rats. One week after surgery, the rats were kindled by electrical stimulation of hippocampus in a rapid manner (12 stimulations/day) for 6 days with sodium valproate alone or combined with low-frequency electrical stimulation (four packages contained 200 monophasic square wave pulses of 0.1-ms duration at 1 Hz, immediately after kindling stimulations). The duration of afterdischarge, maximum latency to stages 4 and 5, and the maximum duration of these stages were recorded by electromadule during kindling. Results: Application of sodium valproate with low-frequency electrical stimulation caused a reduction in cumulative afterdischarge duration. The maximum latency to the onset of stage 5 seizure increased after sodium valproate application alone, without having a significant effect on the fourth stage. Our findings showed reductions in the seizures duration and increasing in the latency times of both stages after the application of sodium valproate with low-frequency electrical stimulation. Conclusion: It seems that usage of sodium valproate with low-frequency electrical stimulation during kindling was more effective to suppress the epileptic activity than its administration alone and may have a critical role on the antiepileptic effects of sodium valproate.

scholarly journals Activation of the Phosphatidylinositol 3-Kinase/Akt Pathway Contributes to Survival of Primary Epithelial Cells Infected with the Periodontal Pathogen Porphyromonas gingivalis

2004 ◽  
Vol 72 (7) ◽  
pp. 3743-3751 ◽  
Author(s):  
Özlem Yilmaz ◽  
Thomas Jungas ◽  
Philippe Verbeke ◽  
David M. Ojcius
Keyword(s):  
Epithelial Cells ◽  
Host Cell ◽  
Porphyromonas Gingivalis ◽  
Periodontal Pathogen ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
Mitochondrial Membrane Depolarization ◽  
Infected Cells ◽  
Phosphatidylinositol 3

ABSTRACT Porphyromonas gingivalis, an important periodontal pathogen, infects primary gingival epithelial cells (GECs). Despite the large number of bacteria that replicate inside the GECs, the host cell remains viable. We demonstrate that P. gingivalis triggers rapid and reversible surface phosphatidylserine exposure through a mechanism requiring caspase activation. However, after 1 day of infection, the bacteria no longer induce phosphatidylserine externalization and instead protect infected cells against apoptosis. Infection exerts its effect at the level of mitochondria, as P. gingivalis also blocks depolarization of the mitochondrial transmembrane potential and cytochrome c release. Interestingly, protein kinase B/Akt is phosphorylated during infection, which can be blocked with the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002. Suppression of the PI3K/Akt pathway following staurosporine treatment results in mitochondrial-membrane depolarization, cytochrome c release, DNA fragmentation, and increased apoptosis of infected GECs. Thus, P. gingivalis stimulates early surface exposure of phosphatidylserine, which could downmodulate the inflammatory response, while also promoting host cell survival through the PI3K/Akt pathway.

Caloric restriction attenuates aging-induced cardiac insulin resistance in male Wistar rats through activation of PI3K/Akt pathway

2019 ◽  
Vol 29 (1) ◽  
pp. 97-105 ◽  
Author(s):  
M. Granado ◽  
S. Amor ◽  
B. Martín-Carro ◽  
L. Guerra-Menéndez ◽  
A. Tejera-Muñoz ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Caloric Restriction ◽  
Wistar Rats ◽  
Akt Pathway ◽  
Male Wistar Rats

scholarly journals Atorvastatin Represses the Angiotensin 2-Induced Oxidative Stress and Inflammatory Response in Dendritic Cells via the PI3K/Akt/Nrf 2 Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Yuanji Ma ◽  
Zhaoyang Chen ◽  
Yunzeng Zou ◽  
Junbo Ge
Keyword(s):  
Oxidative Stress ◽  
Dendritic Cells ◽  
Stress Responses ◽  
Inflammatory Responses ◽  
Akt Pathway ◽  
Related Factor ◽  
Phosphatidylinositol 3 Kinase ◽  
Pi3k Inhibitor Ly294002 ◽  
Anti Inflammatory ◽  
Antigen Presenting

Dendritic cells (DCs), which are highly proficient antigen-presenting cells, play a complex role in both the initiation and progression of atherosclerosis. We tested the hypothesis that the anti-inflammatory and antioxidant effects of atorvastatin may be partly mediated by the phosphatidylinositol 3-kinase/protein kinase B/transcription factor nuclear factor-erythroid 2-related factor 2 (PI3K/Akt/Nrf 2) pathway via the attenuation of DC maturation, thus reducing the inflammatory and oxidative stress responses. This study showed that angiotensin 2 (Ang 2) induced the maturation of DCs, stimulated CD83, CD40, CD80, and CD86 expression, and increased the secretion of IL-12p70, IL-6, and TNF-α. These effects were suppressed by atorvastatin. Atorvastatin also lowered the levels of reactive oxygen species (ROS) and malondialdehyde (MDA), counteracting their initial increases in response to Ang 2 stimulation. Atorvastatin activated Nrf 2 via the PI3K/Akt pathway and thereby promoted Nrf 2 translocation from the cytoplasm to the nucleus in bone marrow-derived dendritic cells (BMDCs), a process that was reversed by the PI3K inhibitor LY294002. Therefore, the regulation of Nrf 2 expression by the PI3K/Akt pathway plays an important role in the regulation of the statin-mediated antioxidant and anti-inflammatory responses in DCs.

Inhibition of glycogenesis in rat muscles partially depleted of glycogen

1991 ◽  
Vol 261 (2) ◽  
pp. C305-C309 ◽  
Author(s):  
J. Gorski ◽  
I. Krawczuk ◽  
M. Gorska ◽  
J. Rutkiewicz
Keyword(s):  
Sciatic Nerve ◽  
Wistar Rats ◽  
Contractile Activity ◽  
Muscle Group ◽  
Glycogen Depletion ◽  
Stomach Tube ◽  
Plantaris Muscle ◽  
Anesthetized Rats ◽  
Male Wistar Rats ◽  
Stimulation Of

This study aimed to examine the extent to which repletion of glycogen in muscles partially depleted of glycogen may be inhibited by contractions and epinephrine. Four experiments were carried out on untrained male Wistar rats. 1) Animals ran 150 min (1,200 m/h) on a treadmill set at +10 degrees incline. After 60, 90, and 120 min of running, they were given glucose (40% solution, 1 ml/100 g) by a stomach tube. 2) Rats ran on a treadmill set as above for 20 min at 3,200 m/h and then 2 h at 800 m/h. 3) In anesthetized rats, gastrocnemius-plantaris muscle group was made to contract isometrically by means of stimulation of the sciatic nerve. The nerve was stimulated with tetanic pulses (7 V, 0.05-ms duration, delivered in 100-ms trains at 100 Hz): first 15 min, 2 pulses/s, then 2 h, 1 pulse/2 s. 4) Epinephrine (0.5 mg/kg) was administered subcutaneously 10 min before onset of stimulation of the sciatic nerve. The nerve was stimulated 15 min with tetanic pulses (as above), 2 pulses/s. Next, rats were rested for 2 h. Level of glycogen was determined in samples of white and red gastrocnemius, plantaris, and soleus. Initial running or stimulation resulted in pronounced glycogen depletion in each muscle. Thereafter, either considerable or full repletion of glycogen occurred in the muscles despite continued contractile activity or the presence of epinephrine. The degree of repletion depended both on the type of muscle and the type of activation of glycogenolysis (running, stimulation of the nerve, epinephrine).(ABSTRACT TRUNCATED AT 250 WORDS)

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