Baicalein protects cortical neurons from β-amyloid (25-35) induced toxicity

Lebeau, Antony; Esclaire, Françoise; Rostène, William; Pélaprat, Didier

doi:10.1097/00001756-200107200-00031

Cited by 90 publications

(65 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In agreement with our previous observations, 33 activation. 18 However, nothing had been reported yet on the consequences of c-Jun downregulation on Ab-induced caspase activation.…”

Section: Blockade Of 12-lox Expression Disrupts a C-jun-dependent Ab-supporting

confidence: 94%

“…28 With regard to 12-LOX, this enzyme was previously shown to mediate both oxidative glutamate toxicity and BSO-induced apoptosis. 23 In a recent study, 33 we showed that baicalein, a 12-LOX inhibitor, protected cortical neurons from Ab-induced apoptosis, suggesting a role for 12-LOX in the apoptotic process triggered by Ab in these cells.…”

Section: Discussionmentioning

confidence: 82%

“…As illustrated in Figure 1b, a 24-h treatment of cortical cells with 25 mM Ab [25][26][27][28][29][30][31][32][33][34][35] increased the percentage of apoptotic cells, as assessed by 4 0 ,6-diamidino-2-phenylindole (DAPI) staining. This proapoptotic effect of Ab was totally suppressed by a 48-h pretreatment of the cells with the 12-LOX antisense oligonucleotide, whereas the sense or the scramble 12-LOX oligonucleotide did not show any protective action (Figure 1b).…”

Section: Resultsmentioning

confidence: 89%

“…32 Using more selective inhibitors, we recently suggested a participation of 12-LOX in apoptosis triggered by Ab in cortical neurons. 33 However, inhibitors can only provide circumstantial evidence about the role of LOXs in Ab-induced toxicity, since most of these compounds also possess other characteristics such as proor antioxidant properties, 25,26,[34][35][36] which might lead to LOX-independent effects. In order to assess the protective potential of 12-LOX blockade towards Ab-induced apoptosis, we used here an antisense oligonucleotide-based strategy.…”

Section: Resultsmentioning

confidence: 99%

“…28 We recently reported that the 5-LOX inhibitor, caffeic acid, did not counteract apoptosis induced by Ab in cortical neurons, suggesting that 5-LOX was not involved in this degeneration process. 33 In the present study, we further evaluated this hypothesis through the same strategy as that used for 12-LOX. As shown in Figure 4a, pretreatment of cortical cells for 48 h with the antisense 5-LOX oligonucleotide induced an important decrease in the expression of the 5-LOX protein.…”

Section: Resultsmentioning

confidence: 99%

See 4 more Smart Citations

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

View full text Add to dashboard Cite

The cyclo-oxygenase (COX) and lipoxygenase (LOX) pathways belong to the eicosanoid synthesis pathway, a major component of the chronic inflammatory process occurring in Alzheimer's disease (AD). Clinical studies reported beneficial effects of COX inhibitors, but little is known about the involvement of LOXs in AD pathogenesis. b-amyloid peptide (Ab) accumulation contributes to neurodegeneration in AD, but mechanisms underlying Ab toxicity have not been fully elucidated yet. Here, using an antisense oligonucleotide-based strategy, we show that blockade of 12-LOX expression prevents both Ab-induced apoptosis and overexpression of c-Jun, a factor required for the apoptotic process, in cortical neurons. Conversely, the 12-LOX metabolite, 12(S)-HETE (12(S)-hydroxy-(5Z, 8Z, 10E, 14Z)-eicosatetraenoic acid), promoted c-Jun-dependent apoptosis. Specificity of the 12-LOX involvement was further supported by the observed lack of contribution of 5-LOX in this process. These data indicate that blockade of 12-LOX expression disrupts a c-Jun-dependent apoptosis pathway, and suggest that 12-LOX may represent a new target for the treatment of AD.

show abstract

“…In agreement with our previous observations, 33 activation. 18 However, nothing had been reported yet on the consequences of c-Jun downregulation on Ab-induced caspase activation.…”

Section: Blockade Of 12-lox Expression Disrupts a C-jun-dependent Ab-supporting

confidence: 94%

Section: Discussionmentioning

confidence: 82%

Section: Resultsmentioning

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

See 3 more Smart Citations

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

et al. 2004

View full text Add to dashboard Cite

show abstract

Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: Functional effect of MCP‐1/CCL2 on calcium mobilization in primary cultured neurons

Banisadr

Gosselin

Mechighel

et al. 2005

J of Comparative Neurology

Self Cite

117

105

View full text Add to dashboard Cite

Chemokines and their receptors are well described in the immune system, where they promote cell migration and activation. In the central nervous system, chemokine has been implicated in neuroinflammatory processes. However, an increasing number of evidence suggests that they have regulatory functions in the normal nervous system, where they could participate in cell communication. In this work, using a semiquantitative immunohistochemistry approach, we provide the first neuroanatomical mapping of constitutive neuronal CCR2 localization. Neuronal expression of CCR2 was observed in the anterior olfactory nucleus, cerebral cortex, hippocampal formation, caudate putamen, globus pallidus, supraoptic and paraventricular hypothalamic nuclei, amygdala, substantia nigra, ventral tegmental area, and in the brainstem and cerebellum. These data are largely in accordance with results obtained using quantitative autoradiography with [(125)I]MCP-1/CCL2 and RT-PCR CCR2 mRNA analysis. Furthermore, using dual fluorescent immunohistochemistry we studied the chemical phenotype of labeled neurons and demonstrated the coexistence of CCR2 with classical neurotransmitters. Indeed, localization of CCR2 immunostaining is observed in dopaminergic neurons in the substantia nigra pars compacta and in the ventral tegmental area as well as in cholinergic neurons in the substantia innominata and caudate putamen. Finally, we show that the preferential CCR2 ligand, MCP-1/CCL2, elicits Ca(2+) transients in primary cultured neurons from various rat brain regions including the cortex, hippocampus, hypothalamus, and mesencephalon. In conclusion, the constitutive neuronal CCR2 expression in selective brain structures suggests that this receptor could be involved in neuronal communication and possibly associated with cholinergic and dopaminergic neurotransmission and related disorders.

show abstract

Small molecule screening in context: Lipid‐catalyzed amyloid formation

2014

View full text Add to dashboard Cite

Islet Amyloid Polypeptide (IAPP) is a 37-residue hormone cosecreted with insulin by the b-cells of the pancreas. Amyloid fiber aggregation of IAPP has been correlated with the dysfunction and death of these cells in type II diabetics. The likely mechanisms by which IAPP gains toxic function include energy independent cell membrane penetration and induction of membrane depolarization. These processes have been correlated with solution biophysical observations of lipid bilayer catalyzed acceleration of amyloid formation. Although the relationship between amyloid formation and toxicity is poorly understood, the fact that conditions promoting one also favor the other suggests related membrane active structural states. Here, a novel high throughput screening protocol is described that capitalizes on this correlation to identify compounds that target membrane active species. Applied to a small library of 960 known bioactive compounds, we are able to report identification of 37 compounds of which 36 were not previously reported as active toward IAPP fiber formation. Several compounds tested in secondary cell viability assays also demonstrate cytoprotective effects. It is a general observation that peptide induced toxicity in several amyloid diseases (such as Alzhiemer's and Parkinson's) involves a membrane bound, preamyloid oligomeric species. Our data here suggest that a screening protocol based on lipid-catalyzed assembly will find mechanistically informative small molecule hits in this subclass of amyloid diseases.

show abstract

Baicalein protects cortical neurons from β-amyloid (25-35) induced toxicity

Cited by 90 publications

References 24 publications

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Blockade of 12-lipoxygenase expression protects cortical neurons from apoptosis induced by β-amyloid peptide

Constitutive neuronal expression of CCR2 chemokine receptor and its colocalization with neurotransmitters in normal rat brain: Functional effect of MCP‐1/CCL2 on calcium mobilization in primary cultured neurons

Small molecule screening in context: Lipid‐catalyzed amyloid formation

Contact Info

Product

Resources

About