scholarly journals Regional distribution of the enzymes of haem biosynthesis and the inhibition of 5-aminolaevulinate synthase by manganese in the rat brain

1980 ◽  
Vol 190 (2) ◽  
pp. 315-321 ◽  
Author(s):  
Mahin D. Maines
Keyword(s):  
Enzyme Activity ◽  
Cerebral Cortex ◽  
Rat Brain ◽  
Metal Ion ◽  
Regional Distribution ◽  
State Level ◽  
Haem Biosynthesis ◽  
The Brain

The activity of 5-aminolaevulinate synthase, the rate-limiting enzyme of haem biosynthesis, is differentially distributed in various regions of the rat brain. The cerebellum possessed the highest enzyme activity of the eight regions studied. The cerebral cortex and the midbrain also exhibited high 5-aminolaevulinate synthase activity; the septum, hypothalamus, thalamus, amygdala and the hippocampus possessed much lower enzyme activity. However, the total porphyrin and haem contents of the different brain segments did not vary greatly. Mn2+, when administered subcutaneously to rats, effectively inhibited the activity of 5-aminolaevulinate synthase in the cerebellum, midbrain and cerebral cortex; however, repeated injections of the metal ion neither decreased the haem and porphyrin contents of the brain nor induced haem oxygenase activity. Mn2+ was not an effective inhibitor of 5-aminolaevulinate synthase activity in vitro. On the other hand, studies carried out with the liver in vivo suggested that Mn2+ may alter the turnover rate of cellular haem and haemoproteins. In that event, it is likely that the inhibition of 5-aminolaevulinate synthase by Mn2+ was in part a result of the inhibition of protein synthesis by the metal ion. It is postulated that the haem and porphyrin contents of the brain are maintained at a steady-state level, due in part to the refractoriness to inducers of the regulatory mechanism for haem catabolic enzymes and in part to the ability of the organ to utilize haem precursors derived from extraneuronal sources.

scholarly journals Regional distribution of SGLT activity in rat brain in vivo

2013 ◽  
Vol 304 (3) ◽  
pp. C240-C247 ◽  
Author(s):  
Amy S. Yu ◽  
Bruce A. Hirayama ◽  
Gerald Timbol ◽  
Jie Liu ◽  
Ana Diez-Sampedro ◽  
...  
Keyword(s):  
Rat Brain ◽  
Ex Vivo ◽  
Osmotic Shock ◽  
Regional Distribution ◽  
The Body ◽  
Specific Substrate ◽  
Ex Vivo Autoradiography ◽  
Molecular Imaging Probe ◽  
The Brain

Na+-glucose cotransporter (SGLT) mRNAs have been detected in many organs of the body, but, apart from kidney and intestine, transporter expression, localization, and functional activity, as well as physiological significance, remain elusive. Using a SGLT-specific molecular imaging probe, α-methyl-4-deoxy-4-[18F]fluoro-d-glucopyranoside (Me-4-FDG) with ex vivo autoradiography and immunohistochemistry, we mapped in vivo the regional distribution of functional SGLTs in rat brain. Since Me-4-FDG is not a substrate for GLUT1 at the blood-brain barrier (BBB), in vivo delivery of the probe into the brain was achieved after opening of the BBB by an established procedure, osmotic shock. Ex vivo autoradiography showed that Me-4-FDG accumulated in regions of the cerebellum, hippocampus, frontal cortex, caudate nucleus, putamen, amygdala, parietal cortex, and paraventricular nucleus of the hypothalamus. Little or no Me-4-FDG accumulated in the brain stem. The regional accumulation of Me-4-FDG overlapped the distribution of SGLT1 protein detected by immunohistochemistry. In summary, after the BBB is opened, the specific substrate for SGLTs, Me-4-FDG, enters the brain and accumulates in selected regions shown to express SGLT1 protein. This localization and the sensitivity of these neurons to anoxia prompt the speculation that SGLTs may play an essential role in glucose utilization under stress such as ischemia. The expression of SGLTs in the brain raises questions about the potential effects of SGLT inhibitors under development for the treatment of diabetes.

Ouabain-induced Seizures in Rats: Regional and Subcellular Localization of 3H-Ouabain Associated with Na+–K+-ATPase in Brain

1972 ◽  
Vol 50 (8) ◽  
pp. 888-896 ◽  
Author(s):  
J. Donaldson ◽  
J. L. Minnich ◽  
A. Barbeau
Keyword(s):  
Subcellular Localization ◽  
Regional Distribution ◽  
Subcellular Fractionation ◽  
Synaptosomal Membrane ◽  
Intraventricular Injections ◽  
The Brain

Previous observations on clonic and tonic seizures in rats induced by intraventricular injections of ouabain, Zn2+, or Cu2+ have been expanded and confirmed. Tritiated ouabain was injected intraventricularly to rats and its regional distribution studied in the brain. The hippocampus and hypothalamus were found to be the regions with highest accumulation of radioactivity. This was supported by the in vitro finding that synaptosomes from both these regions demonstrate the highest uptake of the labelled ouabain. Subcellular fractionation experiments following in vivo injection of 3H-ouabain revealed that maximal radioactivity is associated with synaptosomal membrane fractions rich in Na+–K+-ATPase.

Syzygium cumini (L.) skeels seed extract ameliorates in vitro and in vivo oxidative potentials of the brain cerebral cortex of alcohol-treated rats

2011 ◽  
Vol 12 (1) ◽  
pp. 59-66 ◽  
Author(s):  
Shahdat Hossain ◽  
Asiqur Rahaman ◽  
Taslima Nahar ◽  
Mafroz Ahmed Basunia ◽  
Ferdousi Rahman Mowsumi ◽  
...  
Keyword(s):  
Cerebral Cortex ◽  
Seed Extract ◽  
Syzygium Cumini ◽  
The Brain

Decreased aminotransferase activity of serum and various tissues in the rat after cefazolin treatment.

1979 ◽  
Vol 25 (7) ◽  
pp. 1263-1266 ◽  
Author(s):  
M S Dhami ◽  
R Drangova ◽  
R Farkas ◽  
T Balazs ◽  
G Feuer
Keyword(s):  
Enzyme Activity ◽  
Pyruvate Carboxylase ◽  
Aminotransferase Activity ◽  
Liver And Kidney ◽  
Mixed Function Oxidase System ◽  
The Brain ◽  
Microsomal Mixed Function Oxidase ◽  
Alanine Aminotransferase Activity

Abstract Treatment of rats with cefazolin in vivo significantly suppressed activity of alanine and aspartate aminotransferases in serum and in the liver, brain, kidney, and heart. Simultaneous administration of pyridoxal further reduced enzyme activity except in the liver, where there was no change. Pyridoxal 5'-phosphate partly reversed the decreased enzyme activity in the serum, liver, and kidney, but did not return it to the amount observed in the control animals; enzyme activity remained suppressed in the brain and heart. The effect of cefazolin was dose related, but there was no sex-related difference. In contrast to its action on am-notransferase activity, cefazolin elicited no effect on alkaline phosphatase (pyridoxal-5'-phosphate hydrolase) in serum or on pyruvate carboxylase in the liver, heart, and kidney. Cefazolin exposed to the hepatic microsomal mixed-function oxidase system in vitro was partly converted into metabolites that inhibited serum alanine aminotransferase activity in vitro. The latter inhibition was reversed by the addition of pyridoxal 5'-phosphate.

scholarly journals Activation of PKC Isoform βI at the Blood–Brain Barrier Rapidly Decreases P-Glycoprotein Activity and Enhances Drug Delivery to the Brain

2010 ◽  
Vol 30 (7) ◽  
pp. 1373-1383 ◽  
Author(s):  
Robert R Rigor ◽  
Brian T Hawkins ◽  
David S Miller
Keyword(s):  
Rat Brain ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Capillaries ◽  
P Glycoprotein ◽  
Blood Brain ◽  
Tnf Α ◽  
The Brain

P-glycoprotein is an ATP (adenosine triphosphate)-driven drug efflux transporter that is highly expressed at the blood–brain barrier (BBB) and is a major obstacle to the pharmacotherapy of central nervous system diseases, including brain tumors, neuro-AIDS, and epilepsy. Previous studies have shown that P-glycoprotein transport activity in rat brain capillaries is rapidly reduced by the proinflammatory cytokine, tumor necrosis factor-α (TNF-α) acting through protein kinase C (PKC)-dependent signaling. In this study, we used isolated rat brain capillaries to show that the TNF-α-induced reduction of P-glycoprotein activity was prevented by a PKCβI/II inhibitor, LY333531, and mimicked by a PKCβI/II activator, 12-deoxyphorbol-13-phenylacetate-20-acetate (dPPA). Western blotting of brain capillary extracts with phospho-specific antibodies showed that dPPA activated PKCβI, but not PKCβII. Moreover, in intact rats, intracarotid infusion of dPPA potently increased brain accumulation of the P-glycoprotein substrate, [3H]-verapamil without compromising tight junction integrity. Thus, PKCβI activation selectively reduced P-glycoprotein activity both in vitro and in vivo. Targeting PKCβI at the BBB may prove to be an effective strategy for enhancing the delivery of small molecule therapeutics to the brain.

Tumor treating fields effects on the blood-brain barrier in vitro and in vivo.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2551-2551
Author(s):  
Ellaine Salvador ◽  
Almuth Kessler ◽  
Julia Hoermann ◽  
Dominik Domroese ◽  
Clara Schaeffer ◽  
...  
Keyword(s):  
Rat Brain ◽  
Blood Brain Barrier ◽  
Cell Morphology ◽  
Cns Tumors ◽  
Brain Barrier ◽  
Dce Mri ◽  
Tumor Treating Fields ◽  
The Brain

2551 Background: The greatest hurdle, which even potent and effective drugs targeting central nervous system (CNS) tumors and other disorders face, is the blood brain barrier (BBB). The inability to cross the tight regulatory mechanism renders these drugs futile. Of late, administration of tumor treating fields (TTFields) as part of a combined treatment modality for glioblastoma demonstrated increased overall patient survival. Still, the effects of TTFields on the BBB have not yet been investigated. Here, we report the potential of TTFields application to open up the BBB. Methods: Murine brain endothelial cells were treated with 100-300 kHz TTFields for 24-96 h. Cells were also allowed to recover from 24-96 h after treatment. Subsequently, changes in cell morphology, integrity, and permeability were observed via staining of intercellular junction proteins (IJP) as well as transendothelial electrical resistance (TEER)and permeability assays. In vivo, rats were treated with 100 kHz TTFields or heat for 72 h after which they were IV injected with Evan´s Blue (EB)/ TRITC-dextran (TD) which was later quantified from the brain. Rat brain cryosections were also stained for IJPs as well as immunoglobulin G (IgG) to assess vessel structure. Finally, serial dynamic contrast-enhanced (DCE) MRI with gadolinium (Gd) contrast agent was performed pre- and post- TTFields. Results: Upon TTFields application, IJPs such as claudin-5 were delocalized from the cell membrane to the cytoplasm with maximal effects at 100 kHz. In addition, BBB integrity was significantly reduced and permeability for 4 kDa molecules was significantly increased. Cell morphology recovery was first observed at 48 h post-treatment and completely restored to normal after 96 h, indicating a reversibility of the TTFields effect on the BBB. In addition, EB and TD permeated the rat brain post-TTFields treatment. Brain cryosections displayed IJPs delocalization as well as IgG accumulation in the brain parenchyma. Confirming these observations, increased Gd in the brain was shown by DCE-MRI post-TTFields application. A reversion to normal conditions was detected 96 h after end of treatment, which was demonstrated by no difference in contrast enhancement between control and treated rats. Conclusions: TTFields application both in vitro and in vivo points towards its ability to transiently open the BBB. This presents TTFields as a novel aid for drug delivery geared towards treatment of CNS tumors and other related diseases. Hence, it is indicative of the possibility of an enhanced and more effective combinatorial therapeutic strategy.

Effect of pH and inhibitors on beta-amyloid fibril assembly

1996 ◽  
Vol 54 ◽  
pp. 752-753
Author(s):  
Beverly E. Maleeff ◽  
Timothy K. Hart ◽  
Stephen J. Wood ◽  
Ronald Wetzel
Keyword(s):  
Amyloid Fibril ◽  
Peptide Fragment ◽  
Hydrophobic Peptides ◽  
Amyloid Fibril Formation ◽  
Effects Of Ph ◽  
Severity Of The Disease ◽  
Kinetics Of ◽  
The Brain

Alzheimer's disease is characterized post-mortem in part by abnormal extracellular neuritic plaques found in brain tissue. There appears to be a correlation between the severity of Alzheimer's dementia in vivo and the number of plaques found in particular areas of the brain. These plaques are known to be the deposition sites of fibrils of the protein β-amyloid. It is thought that if the assembly of these plaques could be inhibited, the severity of the disease would be decreased. The peptide fragment Aβ, a precursor of the p-amyloid protein, has a 40 amino acid sequence, and has been shown to be toxic to neuronal cells in culture after an aging process of several days. This toxicity corresponds to the kinetics of in vitro amyloid fibril formation. In this study, we report the biochemical and ultrastructural effects of pH and the inhibitory agent hexadecyl-N-methylpiperidinium (HMP) bromide, one of a class of ionic micellar detergents known to be capable of solubilizing hydrophobic peptides, on the in vitro assembly of the peptide fragment Aβ.

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