Reduced nitric oxide responsive soluble guanylyl cyclase activity in the superior temporal cortex of patients with Alzheimer's disease

Bonkale, Willy L.; Winblad, Bengt; Ravid, Rivka; Cowburn, Richard F.

doi:10.1016/0304-3940(95)11323-o

Cited by 78 publications

(52 citation statements)

References 17 publications

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“…Consistent with these results, the increase of cGMP levels has been found to reduce both A␤-induced cell death (WirtzBrugger and Giovanni, 2000) and vasoactivity (Paris et al, 2000). Moreover, a decrease in cGMP levels has been detected either in vessels and neurons after A␤ treatment or in aged brains (Bonkale et al, 1995;Vallebuona and Raiteri, 1995;Chalimoniuk and Strosznajder, 1998;Paris et al, 1999;Baltrons et al, 2002).…”

Section: Discussionsupporting

confidence: 69%

“…Moreover, BAY41-2272 rescued the A␤-induced LTP impairment, and DEA/NO reestablished the cGMP immunofluorescence increase in tetanized slices exposed to A␤. Interestingly, A␤ decreases sGC expression in brain astroglial cells (Baltrons et al, 2002), and sGC activity is reduced in the superior temporal cortex of AD patients (Bonkale et al, 1995). Therefore, it would be interesting to test in future experiments whether A␤ reduces sGC expression and/or activity in our preparation.…”

Section: Discussionmentioning

confidence: 99%

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Amyloid-β Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity

Puzzo¹,

Vitolo²,

Trinchese³

et al. 2005

J. Neurosci.

222

219

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Amyloid-β Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity

Puzzo¹,

Vitolo²,

Trinchese³

et al. 2005

J. Neurosci.

222

219

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“…Reduction of sGC expression in human glioma tissues and cell lines. sGC expression in glioma cell lines (U87, U251, U373, A172, LN18, LN229, and D54) was examined by Western blot (A) and real time-Q-PCR (B) and compared with that in BE2 human neuroblastoma cell line, which normally expresses both sGC ␣1 and ␤1 subunits at levels similar to those in normal human cortex (D) (Bonkale et al, 1995;Corbalá n et al, 2002;Sharina et al, 2008). The GEO database analysis of sGC gene expression in human glioma tissues of different grade (C) showed that the expression of sGC ␣1 and ␤1 is markedly decreased in astrocytoma (n ϭ 26), oligodendrocytoma (n ϭ 50), and glioblastoma multiforme (n ϭ 81) compared with normal brain tissues (n ϭ 23).…”

Section: Resultsmentioning

confidence: 99%

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Zhu¹,

Li²,

Zheng³

et al. 2011

Mol Pharmacol

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The NO and cGMP signaling pathways are of broad physiological and pathological significance. We compared the NO/soluble guanylyl cyclase (sGC)/cGMP pathway in human glioma tissues and cell lines with that of healthy control samples and demonstrated that sGC expression is significantly lower in glioma preparations. Our analysis of GEO databases (National Cancer Institute) further revealed a statistically significant reduction of sGC transcript levels in human glioma specimens. On the other hand, the expression levels of particulate (membrane) guanylyl cyclases (pGC) and cGMP-specific phosphodiesterase (PDE) were intact in the glioma cells that we have tested. Pharmacologically manipulating endogenous cGMP generation in glioma cells through either stimulating pGC by ANP/BNP, or blocking PDE by 3-isobutyl-1-methylxanthine/ zaprinast caused significant inhibition of proliferation and colony formation of glioma cells. Genetically restoring sGC expression also correlated inversely with glioma cells growth. Orthotopic implantation of glioma cells transfected with an active mutant form of sGC (sGC␣1␤1 Cys105 ) in athymic mice increased the survival time by 4-fold over the control. Histological analysis of xenografts overexpressing ␣1␤1Cys105 sGC revealed changes in cellular architecture that resemble the morphology of normal cells. In addition, a decrease in angiogenesis contributed to glioma inhibition by sGC/cGMP therapy. Our study proposes the new concept that suppressed expression of sGC, a key enzyme in the NO/cGMP pathway, may be associated with an aggressive course of glioma. The sGC/ cGMP signaling-targeted therapy may be a favorable alternative to chemotherapy and radiotherapy for glioma and perhaps other tumors.

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“…This is supported by numerous in vitro studies indicating a role in long-term potentiation (LTP), clustering of presynaptic and postsynaptic proteins (suggesting a role in synaptogenesis), and enhancement of presynaptic neurotransmitter release. Aberrant NO signaling in the brains of AD patients has also been reported (Bonkale et al, 1995). Thus, sGC activation and cGMP formation in the brain may be an effective strategy for mitigating the cognitive dysfunction that occurs as a consequence of cholinergic deficits in the CNS.…”

Section: Introductionmentioning

confidence: 92%

Cognitive Deficits in Rats after Forebrain Cholinergic Depletion are Reversed by a Novel NO Mimetic Nitrate Ester

Bennett

Reynolds

Prusky

et al. 2006

Neuropsychopharmacol

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Many conditions adversely affecting learning, memory, and cognition are associated with reductions in forebrain acetylcholine (ACh), most notably aging and Alzheimer's disease. In the current study, we demonstrate that bilateral depletion of neocortical and hippocampal ACh in rats produces deficits in a spatial learning task and in a recently described, delayed visual matching-to-sample task. Oral administration of the novel nitrate, GT1061 (4-methyl-5-(2-nitroxyethyl) thiazole HCl), and the acetylcholinesterase inhibitor, donepezil, reversed the cognitive deficits in both memory tasks in a dose-dependent manner. GT1061 was superior in the delayed matching-tosample task. GT1061 was absorbed rapidly after oral administration, crossed the blood brain barrier, and achieved brain concentrations that were slightly higher than those found in plasma. The activity of GT1061 was NO mimetic: soluble guanylyl cyclase (sGC) was activated, but selectivity was observed for sGC in the hippocampus relative to the vasculature; and hippocampal levels of phosphorylated ERK1/2, which is a postulated intermediary in the formation of long-term memory, were increased. The beneficial effect on visual and spatial memory task performance supports the concept that stimulating the NO/sGC/cGMP signal transduction system can provide new, effective treatments for cognitive disorders. This approach may be superior to that of current drugs that attempt only to salvage the residual function of damaged cholinergic neurons. Neuropsychopharmacology (2007) 32, 505-513.

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Reduced nitric oxide responsive soluble guanylyl cyclase activity in the superior temporal cortex of patients with Alzheimer's disease

Cited by 78 publications

References 17 publications

Amyloid-β Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity

Amyloid-β Peptide Inhibits Activation of the Nitric Oxide/cGMP/cAMP-Responsive Element-Binding Protein Pathway during Hippocampal Synaptic Plasticity

Restoring Soluble Guanylyl Cyclase Expression and Function Blocks the Aggressive Course of Glioma

Cognitive Deficits in Rats after Forebrain Cholinergic Depletion are Reversed by a Novel NO Mimetic Nitrate Ester

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