Paul Breslin | Rutgers, The State University of New Jersey (original) (raw)

Papers by Paul Breslin

Research paper thumbnail of Smith synthesis of oleocanthal OrgLetters2005 support info2

Research paper thumbnail of Modifying the Bitterness of Selected Oral Pharmaceuticals with Cation and Anion Series of Salts

Pharmaceutical Research, Jul 1, 2002

Research paper thumbnail of A Psychophysical Investigation of Binary Bitter-compound Interactions

Research paper thumbnail of Galindo-Cuspinera Sweet water-taste Nature2006 supplement

Research paper thumbnail of Oral Zinc Sulfate Solutions Inhibit Sweet Taste Perception

Research paper thumbnail of Utilisation d'oleocanthal principal d'irrigation dans l'huile d'olive et composants structuralement et fonctionnellement semblables

Research paper thumbnail of Are Human Taste Thresholds Similar on the Right and Left Sides of the Tongue?

Chemical Senses, Sep 1, 2001

Research paper thumbnail of Suppression of bitterness using sodium salts

Chimia International Journal For Chemistry, Apr 30, 2001

Research paper thumbnail of Cross-adaptation and bitterness inhibition of L-tryptophan, L-phenylalanine and urea: Further support for shared peripheral physiology

Research paper thumbnail of Alzheimer's-associated A oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal

Toxicol Appl Pharmacol, 2009

It now appears likely that soluble oligomers of amyloid-β1–42 peptide, rather than insoluble fibr... more It now appears likely that soluble oligomers of amyloid-β1–42 peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease (AD). Consequently, compounds capable of altering the assembly state of these oligomers (referred to as ADDLs) may have potential for AD therapeutics. Phenolic compounds are of particular interest for their ability to disrupt Aβ oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturally-occurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Aβ species, when assayed with both sequence- and conformation-specific Aβ antibodies, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in MW and a ladder-like distribution of SDS-stable ADDL subspecies. In comparison with control ADDLs, oligomers formed in the presence of OC (Aβ-OC) showed equivalent colocalization at synapses but exhibited greater immunofluorescence as a result of increased antibody recognition. The enhanced signal at synapses was not due to increased synaptic binding, as direct detection of fluorescently-labeled ADDLs showed an overall reduction in ADDL signal in the presence of OC. Decreased binding to synapses was accompanied by significantly less synaptic deterioration assayed by drebrin loss. Additionally, treatment with OC improved antibody clearance of ADDLs. These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics.

Research paper thumbnail of Peyrot Oleocanthal and TRPA1 supplement JNeuroscience2011

Research paper thumbnail of Use of the irritating principal oleocanthal in olive oil, as well as structurally and functionally similar compounds

Research paper thumbnail of Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Sep 1, 1995

Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference... more Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference for NaCl and displays more aversive and fewer ingestive oral motor responses to orally infused NaCl when tested in sodium balance. Despite these differences, F344 rats show an increase in preference for NaCl in response to sodium depletion. The present study was designed to determine whether the salt appetite of sodium-depleted F344 rats is cation specific and whether such selectivity is mediated in part by an intact chorda tympani nerve. Sodium-depleted (10 mg furosemide) F344 (n = 13) and Wistar (n = 16) rats were permitted repeated access to nine stimuli (water, and 0.05 and 0.3 M NaCl, KCl, NH4Cl, and CaCl2), presented randomly in 10-s trials. One-half of the rats had their chorda tympani nerve sectioned (CTX). Under conditions of sodium depletion, both strains discriminated NaCl from other chloride salts. CTX significantly impaired the selectivity of the licking behavior in both strains, suggesting that sodium-specific licking is partially mediated by anterior tongue taste receptors. These findings suggest that both sodium-depleted F344 and Wistar rats are comparable in their abilities to recognize NaCl, to distinguish it from other salts, and to respond selectively to it, despite the fact that sodium-replete F344 and Wistar rats differ greatly in their NaCl preference.

Research paper thumbnail of (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization

Molecular & cellular oncology

(-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been impl... more (-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture and found that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed their proliferation but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins required for lysosomal membrane stability. The data presented here indicate that cancer cells, which tend to have fragile lysosomal membranes compared to non-cancerous cells, are susceptible to cell death induced by lysosomotropic agents. Therefore, targeting lysosomal membrane stability represents a novel approach for the induction of cancer-specific cell death.

Research paper thumbnail of Smith synthesis of oleocanthal OrgLetters2005 support info2

Research paper thumbnail of Flavor Interactions at the Sensory Level

Research paper thumbnail of Modifying the bitterness of selected oral pharmaceuticals with cation and anion series of salts

Pharmaceutical research, 2002

NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purp... more NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purpose of this study was to examine the influence of a variety of cations and anions on the bitterness of selected oral pharmaceuticals and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine, and urea. Human psychophysical taste evaluation using a whole mouth exposure procedure was used. The cations (all associated with the acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to varying degrees. The sodium cation significantly (P < 0.003) inhibited bitterness of the pharmaceuticals more than the other cations. The anions (all associated with the sodium cation) also inhibited bitterness to varying degrees. With the exception of salicylate, the glutamate and adenosine monophosphate anions significantly (P < 0.001) inhibited bitterness of the pharmaceuticals more than the other anions. Also, there were several specific inhibitory interaction...

Research paper thumbnail of Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats

The American journal of physiology, 1993

Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectivel... more Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single-stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of respons...

Research paper thumbnail of Bufe Molecular basis of indiv diffs in bitter CurrBiol2005 supplement

Research paper thumbnail of Suppression of bitterness using sodium salts

Research paper thumbnail of Smith synthesis of oleocanthal OrgLetters2005 support info2

Research paper thumbnail of Modifying the Bitterness of Selected Oral Pharmaceuticals with Cation and Anion Series of Salts

Pharmaceutical Research, Jul 1, 2002

Research paper thumbnail of A Psychophysical Investigation of Binary Bitter-compound Interactions

Research paper thumbnail of Galindo-Cuspinera Sweet water-taste Nature2006 supplement

Research paper thumbnail of Oral Zinc Sulfate Solutions Inhibit Sweet Taste Perception

Research paper thumbnail of Utilisation d'oleocanthal principal d'irrigation dans l'huile d'olive et composants structuralement et fonctionnellement semblables

Research paper thumbnail of Are Human Taste Thresholds Similar on the Right and Left Sides of the Tongue?

Chemical Senses, Sep 1, 2001

Research paper thumbnail of Suppression of bitterness using sodium salts

Chimia International Journal For Chemistry, Apr 30, 2001

Research paper thumbnail of Cross-adaptation and bitterness inhibition of L-tryptophan, L-phenylalanine and urea: Further support for shared peripheral physiology

Research paper thumbnail of Alzheimer's-associated A oligomers show altered structure, immunoreactivity and synaptotoxicity with low doses of oleocanthal

Toxicol Appl Pharmacol, 2009

It now appears likely that soluble oligomers of amyloid-β1–42 peptide, rather than insoluble fibr... more It now appears likely that soluble oligomers of amyloid-β1–42 peptide, rather than insoluble fibrils, act as the primary neurotoxin in Alzheimer's disease (AD). Consequently, compounds capable of altering the assembly state of these oligomers (referred to as ADDLs) may have potential for AD therapeutics. Phenolic compounds are of particular interest for their ability to disrupt Aβ oligomerization and reduce pathogenicity. This study has focused on oleocanthal (OC), a naturally-occurring phenolic compound found in extra-virgin olive oil. OC increased the immunoreactivity of soluble Aβ species, when assayed with both sequence- and conformation-specific Aβ antibodies, indicating changes in oligomer structure. Analysis of oligomers in the presence of OC showed an upward shift in MW and a ladder-like distribution of SDS-stable ADDL subspecies. In comparison with control ADDLs, oligomers formed in the presence of OC (Aβ-OC) showed equivalent colocalization at synapses but exhibited greater immunofluorescence as a result of increased antibody recognition. The enhanced signal at synapses was not due to increased synaptic binding, as direct detection of fluorescently-labeled ADDLs showed an overall reduction in ADDL signal in the presence of OC. Decreased binding to synapses was accompanied by significantly less synaptic deterioration assayed by drebrin loss. Additionally, treatment with OC improved antibody clearance of ADDLs. These results indicate oleocanthal is capable of altering the oligomerization state of ADDLs while protecting neurons from the synaptopathological effects of ADDLs and suggest OC as a lead compound for development in AD therapeutics.

Research paper thumbnail of Peyrot Oleocanthal and TRPA1 supplement JNeuroscience2011

Research paper thumbnail of Use of the irritating principal oleocanthal in olive oil, as well as structurally and functionally similar compounds

Research paper thumbnail of Sodium specificity of salt appetite in Fischer-344 and Wistar rats is impaired by chorda tympani nerve transection

American Journal of Physiology Regulatory Integrative and Comparative Physiology, Sep 1, 1995

Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference... more Unlike other rat strains, the sodium-replete Fischer-344 (F344) strain shows no innate preference for NaCl and displays more aversive and fewer ingestive oral motor responses to orally infused NaCl when tested in sodium balance. Despite these differences, F344 rats show an increase in preference for NaCl in response to sodium depletion. The present study was designed to determine whether the salt appetite of sodium-depleted F344 rats is cation specific and whether such selectivity is mediated in part by an intact chorda tympani nerve. Sodium-depleted (10 mg furosemide) F344 (n = 13) and Wistar (n = 16) rats were permitted repeated access to nine stimuli (water, and 0.05 and 0.3 M NaCl, KCl, NH4Cl, and CaCl2), presented randomly in 10-s trials. One-half of the rats had their chorda tympani nerve sectioned (CTX). Under conditions of sodium depletion, both strains discriminated NaCl from other chloride salts. CTX significantly impaired the selectivity of the licking behavior in both strains, suggesting that sodium-specific licking is partially mediated by anterior tongue taste receptors. These findings suggest that both sodium-depleted F344 and Wistar rats are comparable in their abilities to recognize NaCl, to distinguish it from other salts, and to respond selectively to it, despite the fact that sodium-replete F344 and Wistar rats differ greatly in their NaCl preference.

Research paper thumbnail of (-)-Oleocanthal rapidly and selectively induces cancer cell death via lysosomal membrane permeabilization

Molecular & cellular oncology

(-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been impl... more (-)-Oleocanthal (OC), a phenolic compound present in extra-virgin olive oil (EVOO), has been implicated in the health benefits associated with diets rich in EVOO. We investigated the effect of OC on human cancer cell lines in culture and found that OC induced cell death in all cancer cells examined as rapidly as 30 minutes after treatment in the absence of serum. OC treatment of non-transformed cells suppressed their proliferation but did not cause cell death. OC induced both primary necrotic and apoptotic cell death via induction of lysosomal membrane permeabilization (LMP). We provide evidence that OC promotes LMP by inhibiting acid sphingomyelinase (ASM) activity, which destabilizes the interaction between proteins required for lysosomal membrane stability. The data presented here indicate that cancer cells, which tend to have fragile lysosomal membranes compared to non-cancerous cells, are susceptible to cell death induced by lysosomotropic agents. Therefore, targeting lysosomal membrane stability represents a novel approach for the induction of cancer-specific cell death.

Research paper thumbnail of Smith synthesis of oleocanthal OrgLetters2005 support info2

Research paper thumbnail of Flavor Interactions at the Sensory Level

Research paper thumbnail of Modifying the bitterness of selected oral pharmaceuticals with cation and anion series of salts

Pharmaceutical research, 2002

NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purp... more NaCl has proven to be an effective bitterness inhibitor, but the reason remains unclear. The purpose of this study was to examine the influence of a variety of cations and anions on the bitterness of selected oral pharmaceuticals and bitter taste stimuli: pseudoephedrine, ranitidine, acetaminophen, quinine, and urea. Human psychophysical taste evaluation using a whole mouth exposure procedure was used. The cations (all associated with the acetate anion) inhibited bitterness when mixed with pharmaceutical solutions to varying degrees. The sodium cation significantly (P < 0.003) inhibited bitterness of the pharmaceuticals more than the other cations. The anions (all associated with the sodium cation) also inhibited bitterness to varying degrees. With the exception of salicylate, the glutamate and adenosine monophosphate anions significantly (P < 0.001) inhibited bitterness of the pharmaceuticals more than the other anions. Also, there were several specific inhibitory interaction...

Research paper thumbnail of Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats

The American journal of physiology, 1993

Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectivel... more Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single-stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of respons...

Research paper thumbnail of Bufe Molecular basis of indiv diffs in bitter CurrBiol2005 supplement

Research paper thumbnail of Suppression of bitterness using sodium salts