antibiotic-cv-1 and Disease-Models--Animal

Herein proteomic profiling of the rat hippocampus from the kindling and pilocarpine models of epilepsy was performed to achieve new potential targets for treating epileptic seizures. A total of 144 differently expressed proteins in both left and right hippocampi by two-dimensional electrophoresis coupled to matrix-assisted laser desorption-mass spectrometry were identified across the rat models of epilepsy. Based on network analysis, the majority of differentially expressed proteins were associated with Ca

Topics: ADP-ribosyl Cyclase; Animals; Calcium; Cyclic ADP-Ribose; Disease Models, Animal; Electrophoresis; Epilepsy; Hippocampus; Homeostasis; Kindling, Neurologic; Male; Molecular Targeted Therapy; Pilocarpine; Proteomics; Rats, Wistar; Receptors, Lysophosphatidic Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Synaptosomal-Associated Protein 25

The transient receptor potential melastatin-2 (TRPM2) channel belongs to the transient receptor potential channel superfamily and is a cation channel permeable to Na

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Blood Urea Nitrogen; Calcium Channel Blockers; Catalase; Creatinine; Cyclic ADP-Ribose; Cytoprotection; Disease Models, Animal; Hydrogen Peroxide; Inflammation Mediators; Kidney; Kidney Diseases; Male; Nifedipine; Oxidative Stress; Rats, Wistar; Reperfusion Injury; Signal Transduction; TRPM Cation Channels

The CD38/cADPR pathway has been found to play roles in various inflammatory conditions. However, whether CD38 plays a protective or detrimental effect in the central nervous system (CNS) is controversial. The aim of this study was to determine the effect of CD38/cADPR pathway in sepsis associated brain injury.. Male Sprague-Dawley rats were undergone cecal ligation and puncture (CLP) or sham laparotomies. NAD. NAD. In this study, we found that the CD38/cADPR pathway was activated in sepsis associated brain injury. Blocking this pathway protected the hippocampus from apoptosis, oxidative stress and ultrastructural morphology damages in septic rats.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Animals; Apoptosis; Brain Injuries; Cecum; Cyclic ADP-Ribose; Disease Models, Animal; Hippocampus; Male; Membrane Glycoproteins; Oxidative Stress; Rats; Rats, Sprague-Dawley; Sepsis; Superoxide Dismutase

Although the nicotinamide adenine dinucleotide (NAD(+))/CD38/cyclic ADP ribose (cADPR)/Ca(2+) signaling pathway has been shown to regulate intracellular calcium homeostasis and functions in multiple inflammatory processes, its role in sepsis remains unknown. The aim of this study was to determine whether the NAD(+)/CD38/cADPR/Ca(2+) signaling pathway is activated during sepsis and whether an inhibitor of this pathway, 8-Br-cADPR, protects the organs from sepsis-induced damage.. Male Sprague-Dawley rats were subjected to cecal ligation and puncture (CLP) or sham laparotomies. NAD(+), cADPR, CD38, and intracellular Ca(2+) levels were measured in the hearts, livers, and kidneys of septic rats at 0, 6, 12, 24, and 48 h after CLP surgery. Rats were also divided into sham, CLP, and CLP+8-Br-cADPR groups, and the hearts, livers, and kidneys were hematoxylin-eosin-stained and assayed for malondialdehyde and superoxide dismutase activities.. NAD(+), cADPR, CD38, and intracellular Ca(2+) levels increased in the hearts, livers, and kidneys of septic rats as early as 6-24 h after CLP surgery. Treatment with 8-Br-cADPR inhibited sepsis-induced intracellular Ca(2+) mobilization, attenuated tissue injury, reduced malondialdehyde levels, and increased superoxide dismutase activity in septic rats.. The NAD(+)/CD38/cADPR/Ca(2+) signaling pathway was activated during sepsis in the CLP rat model. Blocking this pathway with 8-Br-cADPR protected hearts, livers, and kidneys from sepsis-induced damage.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Animals; Calcium; Calcium Signaling; Cyclic ADP-Ribose; Disease Models, Animal; Drug Evaluation, Preclinical; Male; Malondialdehyde; Membrane Glycoproteins; Multiple Organ Failure; NAD; Random Allocation; Rats, Sprague-Dawley; Sepsis; Superoxide Dismutase

The present study has been designed to expound the significance of cyclic adenosine diphosphoribose receptor activation in ischemic preconditioning induced reversal of ischemia and reperfusion induced cerebral injury in mice. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water-maze test. Rota-rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) prevented markedly ischemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of memory and motor coordination. 8-Bromo-cyclic adenosine diphosphate ribose (2 mg/kg, ip), an antagonist of cyclic ADP-ribose receptor, attenuated the neuroprotective effect of ischemic preconditioning. It is concluded that neuroprotective effect of ischemic preconditioning may be due to the adenosine diphosphoribose receptor activation.

Topics: Animals; Brain; Brain Infarction; Carotid Stenosis; Cyclic ADP-Ribose; Cytoprotection; Disease Models, Animal; Female; Hypoxia-Ischemia, Brain; Ischemic Preconditioning; Male; Memory Disorders; Mice; Movement Disorders; Neuropsychological Tests; Receptors, Cell Surface; Reperfusion Injury

Here, we report the discovery of a small molecule inhibitor, 2,2'-dihydroxyazobenzene (DAB), of ADP ribosyl cyclase (ADPR-cyclase) and showed that this inhibitor attenuated angiotensin (Ang) II-induced hypertrophic responses.. and results The intracellular concentration of free Ca(2+) [Ca(2+)](i) in adult rat cardiomyocytes was measured by using a confocal microscope. Cardiac hypertrophy was induced by the two-kidney one-clip (2K1C) method. Hypertrophy was determined by de novo protein synthesis, cell volume, echocardiography, nuclear translocation of nuclear factor of activated T-cells, and transforming growth factor-beta1 protein expression. Treatment of cardiomyocytes with Ang II generated a biphasic [Ca(2+)](i) increase that included an initial Ca(2+)peak and sustained Ca(2+) rise via inositol trisphosphate and cyclic ADP-ribose (cADPR) formation, respectively. A cADPR antagonistic analogue, 8-Br-cADPR, and an ADPR-cyclase inhibitor, DAB, blocked the sustained Ca(2+) signal, but not the initial Ca(2+) rise. Furthermore, DAB significantly inhibited Ang II-mediated cADPR formation and hypertrophic responses in vitro. Echocardiography and histological examination revealed significant cardiac hypertrophy in 2K1C rats that was potently inhibited by treatment with DAB. In addition, the hypertrophic responses induced by Ang II in vitro were significantly increased by 2K1C, and DAB treatment reversed these hypertrophic responses to the levels of sham Control.. ADPR-cyclase is an important mediator of cardiac hypertrophy, and inhibition of ADPR-cyclase by DAB may provide a new therapeutic strategy for cardiac diseases.

Topics: ADP-ribosyl Cyclase; Angiotensin II; Animals; Azo Compounds; Calcium; Calcium Signaling; Cardiomegaly; Cell Size; Cyclic ADP-Ribose; Disease Models, Animal; Enzyme Inhibitors; Hypertension, Renovascular; Male; Myocytes, Cardiac; Nephrectomy; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt; Rats; Rats, Sprague-Dawley; Renal Artery; src-Family Kinases