Acute alcohol intoxication decreases cell proliferation and nitric oxide synthase expression in dentate gyrus of rats

Reelin is an extracellular matrix protein expressed in several interneuron subtypes in the hippocampus and dentate gyrus. Neuronal nitric oxide synthase (nNOS) is also expressed by interneurons in these areas. We investigated whether reelin and nNOS are co-localized in the same population of hippocampal interneurons, and whether this colocalization is altered in the heterozygous reeler mouse. We found colocalization of nNOS in reelin-positive cells in the CA1 stratum radiatum and lacunosum moleculare, the CA3 stratum radiatum, and the dentate gyrus subgranular zone, molecular layer, and hilus. In heterozygous reeler mice, the colocalization of nNOS in reelin-positive cells was significantly decreased only in the subgranular zone and molecular layer. The coexpression of reelin and nNOS in several hippocampal regions suggests that reelin and nNOS may work synergistically to promote glutamatergic function, and the loss of this coexpression in heterozygous reeler mice may underlie some of the behavioral deficits observed in these animals.

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Intronic microRNA suppresses endothelial nitric oxide synthase expression and endothelial cell proliferation via inhibition of STAT3 signaling

Molecular and Cellular Biochemistry ◽

10.1007/s11010-011-0870-x ◽

2011 ◽

Vol 357 (1-2) ◽

pp. 9-19 ◽

Cited By ~ 13

Author(s):

Limei Yan ◽

Hong Hao ◽

Terry S. Elton ◽

Zhenguo Liu ◽

Hesheng Ou

Keyword(s):

Nitric Oxide ◽

Cell Proliferation ◽

Endothelial Cell ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Endothelial Cell Proliferation ◽

Stat3 Signaling ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

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Propofol Depresses Angiotensin II–induced Cell Proliferation in Rat Cardiac Fibroblasts

Anesthesiology ◽

10.1097/01.anes.0000365960.74268.21 ◽

2010 ◽

Vol 112 (1) ◽

pp. 108-118 ◽

Cited By ~ 15

Author(s):

Tzu-Hurng Cheng ◽

Yuk-Man Leung ◽

Chi-Wai Cheung ◽

Cheng-Hsien Chen ◽

Yen-Ling Chen ◽

...

Keyword(s):

Nitric Oxide ◽

Cell Proliferation ◽

Protein Kinase ◽

Nitric Oxide Synthase ◽

Endothelial Nitric Oxide Synthase ◽

Protein Kinase B ◽

Cardiac Fibroblasts ◽

Ang Ii ◽

Oxide Synthase ◽

Endothelial Nitric Oxide

Background Propofol may have beneficial effects on the prevention of angiotensin II (Ang II)-induced cardiac fibroblast proliferation via its antioxidative properties. The authors hypothesized that propofol may alter Ang II-induced cell proliferation and aimed to identify the putative underlying signaling pathways in rat cardiac fibroblasts. Methods Cultured rat cardiac fibroblasts were pretreated with propofol then stimulated with Ang II; cell proliferation and endothelin-1 gene expression were examined. The effect of propofol on Ang II-induced nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity were also examined. The effect of propofol on nitric oxide production and protein kinase B and endothelial nitric oxide synthase phosphorylations were also tested to elucidate the intracellular mechanism of propofol in proliferation. Results Ang II (100 nm) increased cell proliferation and endothelin-1 expression, which were partially inhibited by propofol (10 or 30 microm). Propofol also inhibited Ang II-increased nicotinamide adenine dinucleotide phosphate-oxidase activity, reactive oxygen species formation, extracellular signal-regulated kinase phosphorylation, and activator protein 1-mediated reporter activity. Propofol was also found to increase nitric oxide generation and protein kinase B and nitric oxide synthase phosphorylations. Nitric oxide synthase inhibitor (N-nitro-L-arginine methylester) and the short interfering RNA transfection for protein kinase B or endothelial nitric oxide synthase markedly attenuated the inhibitory effect of propofol on Ang II-induced cell proliferation. Conclusions The authors' results suggest that propofol prevents cardiac fibroblast proliferation by interfering with the generation of reactive oxygen species and involves the activation of the protein kinase B-endothelial nitric oxide synthase-nitric oxide pathway.

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Therapeutic effect of and mechanisms underlying the effect of miR-195-5p on subarachnoid hemorrhage-induced vasospasm and brain injury in rats

PeerJ ◽

10.7717/peerj.11395 ◽

2021 ◽

Vol 9 ◽

pp. e11395

Author(s):

Tai-Hsin Tsai ◽

Chih-Hui Chang ◽

Szu-Huai Lin ◽

Yu-Feng Su ◽

Yi-Cheng Tsai ◽

...

Keyword(s):

Nitric Oxide ◽

Cell Death ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Nitric Oxide Synthase ◽

Dentate Gyrus ◽

Basilar Artery ◽

Early Brain Injury ◽

Cell Death Assay ◽

Oxide Synthase

Objectives There is much evidence suggesting that inflammation contributes majorly to subarachnoid hemorrhage (SAH)-induced cerebral vasospasm and brain injury. miRNAs have been found to modulate inflammation in several neurological disorders. This study investigated the effect of miR-195-5p on SAH-induced vasospasm and early brain injury in experimental rats. Methods Ninety-six Sprague-Dawley male rats were randomly and evenly divided into a control group (no SAH, sham surgery), a SAH only group, a SAH + NC-mimic group, and a SAH + miR-195-5p group. SAH was induced using a single injection of blood into the cisterna magna. Suspensions containing NC-mimic and miR-195-5p were intravenously injected into rat tail 30 mins after SAH was induced. We determined degree of vasospasm by averaging areas of cross-sections the basilar artery 24h after SAH. We measured basilar artery endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κ B), phosphorylated NF-κ B (p-NF-κ B), inhibitor of NF-κ B (Iκ Bα) and phosphorylated-Iκ Bα (p-Iκ Bα). Cell death assay was used to quantify the DNA fragmentation, an indicator of apoptotic cell death, in the cortex, hippocampus, and dentate gyrus. Tumor necrosis factor alpha (TNF-α) levels were measured using sample protein obtained from the cerebral cortex, hippocampus and dentate gyrus. Results Prior to fixation by perfusion, there were no significant physiological differences among the control and treatment groups. SAH successfully induced vasospasm and early brain injury. MiR-195-5p attenuated vasospasam-induced changes in morphology, reversed SAH-induced elevation of iNOS, p-NF-κ B, NF-κ B, and p-Iκ Bα and reversed SAH-induced suppression of eNOS in the basilar artery. Cell death assay revealed that MiR-195-5p significantly decreased SAH-induced DNA fragmentation (apoptosis) and restored TNF-α level in the dentate gyrus. Conclusion In conclusion, MiRNA-195-5p attenuated SAH-induced vasospasm by up-regulating eNOS, down-regulating iNOS and inhibiting the NF-κ B signaling pathway. It also protected neurons by decreasing SAH-induced apoptosis-related cytokine TNF-α expression in the dentate gyrus. Further study is needed to elucidate the detail mechanism underlying miR-195-5p effect on SAH-induced vasospasm and cerebral injury. We believe that MiR-195-5p can potentially be used to manage SAH-induced cerebral vasospasm and brain injury.

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