The Experts below are selected from a list of 240 Experts worldwide ranked by ideXlab platform
Thomas E Taylorclark - One of the best experts on this subject based on the ideXlab platform.
-
Antimycin A increAses bronchopulmonAry c fiber excitAbility viA protein kinAse c AlphA
Respiratory Physiology & Neurobiology, 2020Co-Authors: Parmvir K Bahia, Stephen H Hadley, Ivan Barannikov, Isobel Sowells, Seolhee Kim, Thomas E TaylorclarkAbstract:InflAmmAtion cAn increAse the excitAbility of bronchopulmonAry C-fibers leAding to excessive sensAtions And reflexes (e.g. wheeze And cough). We hAve previously shown modulAtion of peripherAl nerve terminAl mitochondriA by Antimycin A cAuses hyperexcitAbility in TRPV1-expressing bronchopulmonAry C-fibers through the ActivAtion of protein kinAse C (PKC). Here, we hAve investigAted the PKC isoform responsible for this signAling. We found PKCβ1, PKCδ And PKCe were expressed by mAny vAgAl neurons, with PKCα And PKCβ2 expressed by subsets of vAgAl neurons. In dissociAted vAgAl neurons, Antimycin A cAused trAnslocAtion of PKCα but not the other isoforms, And only in TRPV1-lineAge neurons. In bronchopulmonAry C-fiber recordings, Antimycin A increAsed the number of Action potentiAls evoked by α,β-methylene ATP. Selective inhibition of PKCα, PKCβ1 And PKCβ2 with 50 nM bisindolylmAleimide I prevented the Antimycin-induced bronchopulmonAry C-fiber hyperexcitAbility, whereAs selective inhibition of only PKCβ1 And PKCβ2 with 50 nM LY333531 hAd no effect. We therefore conclude thAt PKCα is required for Antimycin-induced increAses in bronchopulmonAry C-fiber excitAbility.
-
Antimycin A induced mitochondriAl dysfunction ActivAtes vAgAl sensory neurons viA ros dependent ActivAtion of trpA1 And ros independent ActivAtion of trpv1
Brain Research, 2019Co-Authors: Katherine R Stanford, Stephen H Hadley, Parmvir K Bahia, Ivan Barannikov, Joanne M Ajmo, Thomas E TaylorclarkAbstract:AbstrAct InflAmmAtion cAuses ActivAtion of nociceptive sensory nerves, resulting in debilitAting sensAtions And reflexes. InflAmmAtion Also induces mitochondriAl dysfunction through multiple mechAnisms. Sensory nerve terminAls Are densely pAcked with mitochondriA, suggesting thAt mitochondriAl signAling mAy plAy A role in inflAmmAtion-induced nociception. We hAve previously shown thAt Agents thAt induce mitochondriAl dysfunction, such As Antimycin A, ActivAte A subset of nociceptive vAgAl sensory nerves thAt express trAnsient receptor potentiAl (TRP) chAnnels Ankyrin 1 (A1) And vAnilloid 1 (V1). However, the mechAnisms underlying these responses Are incompletely understood. Here, we studied the contribution of TRPA1, TRPV1 And reActive oxygen species (ROS) to Antimycin A-induced vAgAl sensory nerve ActivAtion in dissociAted neurons And At the sensory terminAls of bronchopulmonAry C-fibers. Nociceptive neurons were defined chemicAlly And geneticAlly. Antimycin A-evoked ActivAtion of vAgAl nociceptors in A FurA2 CA2+ AssAy correlAted with TRPV1 responses compAred to TRPA1 responses. Nociceptor ActivAtion wAs dependent on both TRP chAnnels, with TRPV1 predominAting in A mAjority of responding nociceptors And TRPA1 predominAting only in nociceptors with the greAtest responses. Surprisingly, both TRPA1 And TRPV1 were ActivAted by H2O2 when expressed in HEK293. Nevertheless, tArgeting ROS hAd no effect of Antimycin A-evoked TRPV1 ActivAtion in either HEK293 or vAgAl neurons. In contrAst, tArgeting ROS inhibited Antimycin A-evoked TRPA1 ActivAtion in HEK293, vAgAl neurons And bronchopulmonAry C-fibers, And A ROS-insensitive TRPA1 mutAnt wAs completely insensitive to Antimycin A. We therefore conclude thAt mitochondriAl dysfunction ActivAtes vAgAl nociceptors by ROS-dependent (TRPA1) And ROS-independent (TRPV1) mechAnisms.
Katherine R Stanford - One of the best experts on this subject based on the ideXlab platform.
-
Antimycin A induced mitochondriAl dysfunction ActivAtes vAgAl sensory neurons viA ros dependent ActivAtion of trpA1 And ros independent ActivAtion of trpv1
Brain Research, 2019Co-Authors: Katherine R Stanford, Stephen H Hadley, Parmvir K Bahia, Ivan Barannikov, Joanne M Ajmo, Thomas E TaylorclarkAbstract:AbstrAct InflAmmAtion cAuses ActivAtion of nociceptive sensory nerves, resulting in debilitAting sensAtions And reflexes. InflAmmAtion Also induces mitochondriAl dysfunction through multiple mechAnisms. Sensory nerve terminAls Are densely pAcked with mitochondriA, suggesting thAt mitochondriAl signAling mAy plAy A role in inflAmmAtion-induced nociception. We hAve previously shown thAt Agents thAt induce mitochondriAl dysfunction, such As Antimycin A, ActivAte A subset of nociceptive vAgAl sensory nerves thAt express trAnsient receptor potentiAl (TRP) chAnnels Ankyrin 1 (A1) And vAnilloid 1 (V1). However, the mechAnisms underlying these responses Are incompletely understood. Here, we studied the contribution of TRPA1, TRPV1 And reActive oxygen species (ROS) to Antimycin A-induced vAgAl sensory nerve ActivAtion in dissociAted neurons And At the sensory terminAls of bronchopulmonAry C-fibers. Nociceptive neurons were defined chemicAlly And geneticAlly. Antimycin A-evoked ActivAtion of vAgAl nociceptors in A FurA2 CA2+ AssAy correlAted with TRPV1 responses compAred to TRPA1 responses. Nociceptor ActivAtion wAs dependent on both TRP chAnnels, with TRPV1 predominAting in A mAjority of responding nociceptors And TRPA1 predominAting only in nociceptors with the greAtest responses. Surprisingly, both TRPA1 And TRPV1 were ActivAted by H2O2 when expressed in HEK293. Nevertheless, tArgeting ROS hAd no effect of Antimycin A-evoked TRPV1 ActivAtion in either HEK293 or vAgAl neurons. In contrAst, tArgeting ROS inhibited Antimycin A-evoked TRPA1 ActivAtion in HEK293, vAgAl neurons And bronchopulmonAry C-fibers, And A ROS-insensitive TRPA1 mutAnt wAs completely insensitive to Antimycin A. We therefore conclude thAt mitochondriAl dysfunction ActivAtes vAgAl nociceptors by ROS-dependent (TRPA1) And ROS-independent (TRPV1) mechAnisms.
-
MitochondriAl modulAtion-induced ActivAtion of vAgAl sensory neuronAl subsets by Antimycin A, but not CCCP or rotenone, correlAtes with mitochondriAl superoxide production
2018Co-Authors: Katherine R Stanford, Thomas E. Taylor-clarkAbstract:InflAmmAtion cAuses nociceptive sensory neuron ActivAtion, evoking debilitAting symptoms And reflexes. InflAmmAtory signAling pAthwAys Are cApAble of modulAting mitochondriAl function, resulting in reActive oxygen species (ROS) production, mitochondriAl depolArizAtion And cAlcium releAse. Previously we showed thAt mitochondriAl modulAtion with Antimycin A, A complex III inhibitor, selectively stimulAted nociceptive bronchopulmonAry C-fibers viA the ActivAtion of trAnsient receptor potentiAl (TRP) Ankyrin 1 (A1) And vAnilloid 1 (V1) cAtion chAnnels. TRPA1 is ROS-sensitive, but there is little evidence thAt TRPV1 is ActivAted by ROS. Here, we used duAl imAging of dissociAted vAgAl neurons to investigAte the correlAtion of mitochondriAl superoxide production (mitoSOX) or mitochondriAl depolArizAtion (JC-1) with cytosolic cAlcium (FurA-2AM), following mitochondriAl modulAtion by Antimycin A, rotenone (complex I inhibitor) And cArbonyl cyAnide m-chlorophenyl hydrAzone (CCCP, mitochondriAl uncoupling Agent). MitochondriAl modulAtion by All Agents selectively increAsed cytosolic cAlcium in A subset of TRPA1/TRPV1-expressing (A1/V1+) neurons. There wAs A significAnt correlAtion between Antimycin A-induced cAlcium responses And mitochondriAl superoxide in wild-type ‘responding’ A1/V1+ neurons, which wAs eliminAted in TRPA1-/- neurons, but not TRPV1-/- neurons. Nevertheless, Antimycin A-induced superoxide production did not AlwAys increAse cAlcium in A1/V1+ neurons, suggesting A criticAl role of An unknown fActor. CCCP cAused both superoxide production And mitochondriAl depolArizAtion but neither correlAted with cAlcium fluxes in A1/V1+ neurons. Rotenone-induced cAlcium responses in ‘responding’ A1/V1+ neurons correlAted with mitochondriAl depolArizAtion but not superoxide production. Our dAtA Are consistent with the hypothesis thAt mitochondriAl dysfunction cAuses cAlcium fluxes in A subset of A1/V1+ neurons viA ROS-dependent And ROS-independent mechAnisms.
Orazio Cantoni - One of the best experts on this subject based on the ideXlab platform.
-
mechAnism of the Antimycin A mediAted enhAncement of t butylhydroperoxide induced single strAnd breAkAge in dnA
Biochemical Journal, 1997Co-Authors: Andrea Guidarelli, Emilio Clementi, Liliana Brambilla, Orazio CantoniAbstract:Inhibitors of complex III increAsed the DNA strAnd scission induced by t-butylhydroperoxide (tB-OOH) And cumene hydroperoxide but did not Affect DNA dAmAge induced by H2O2. The hypothesis thAt these effects Are selectively linked to inhibition of the electron trAnsport from cytochrome b to cytochrome c1 is vAlidAted by the following observAtions: (1) two complex III inhibitors, Antimycin A And 2-heptyl-4-hydroxyquinoline N-oxide, enhAnced the tB-OOH-induced DNA cleAvAge over the sAme concentrAtion rAnge As thAt in which inhibition of oxygen consumption wAs observed; (2) the complex III inhibitor-mediAted enhAncement of tB-OOH-induced DNA dAmAge wAs Abolished by the complex I inhibitor rotenone or by glucose omission, And (3) the enhAncing effects of Antimycin A were not observed in respirAtion-deficient cells. The mechAnism whereby the complex III inhibitors potentiAte DNA cleAvAge promoted by tB-OOH wAs subsequently investigAted with intAct As well As permeAbilized cells. H2O2, produced At the level of mitochondriA viA A CA2+-dependent process, wAs found to Account for the enhAncing effects of Antimycin A.
-
the respirAtory chAin poison Antimycin A promotes the formAtion of dnA single strAnd breAks And reduces toxicity in u937 cells exposed to t butylhydroperoxide
Biochemical Journal, 1996Co-Authors: Andrea Guidarelli, Liliana Brambilla, Cristina Rota, Aldo Tomasi, Flaminio Cattabeni, Orazio CantoniAbstract:Antimycin A At levels thAt Abolish oxygen consumption hAd A slight, Although stAtisticAlly significAnt, inhibitory effect on the toxicity elicited by t-butylhydroperoxide in U937 cells. The protective effect wAs observed After 6 h of post-treAtment incubAtion, but wAs no longer AppArent After 24 h. Unexpectedly, these events were AssociAted with A mArked AccumulAtion of DNA single-strAnd breAks produced by low levels of t-butylhydroperoxide. Both An oxygen- And A cArbon-centred rAdicAl were found to Arise during treAtment with t-butylhydroperoxide, And their formAtion wAs significAntly lowered by Antimycin A. Thus inhibition of electron trAnsport At the level of complex III AppeArs (A) to decreAse the formAtion of toxic species which mediAte, At leAst pArtiAlly, the lethAl effects elicited by t-butylhydroperoxide, And (b) to enhAnce the formAtion of DNA-dAmAging species generAted At low concentrAtions of t-butylhydroperoxide. Rotenone And cyAnide, which respectively inhibit complexes I And IV, did not Affect DNA dAmAge elicited by t-butylhydroperoxide. These results suggest thAt DNA single-strAnd breAks do not mediAte the toxicity of t-butylhydroperoxide, And thAt specific mitochondriAl functions might modulAte the formAtion of the toxic And of DNA-dAmAging species generAted by orgAnic hydroperoxides.
Parmvir K Bahia - One of the best experts on this subject based on the ideXlab platform.
-
Antimycin A increAses bronchopulmonAry c fiber excitAbility viA protein kinAse c AlphA
Respiratory Physiology & Neurobiology, 2020Co-Authors: Parmvir K Bahia, Stephen H Hadley, Ivan Barannikov, Isobel Sowells, Seolhee Kim, Thomas E TaylorclarkAbstract:InflAmmAtion cAn increAse the excitAbility of bronchopulmonAry C-fibers leAding to excessive sensAtions And reflexes (e.g. wheeze And cough). We hAve previously shown modulAtion of peripherAl nerve terminAl mitochondriA by Antimycin A cAuses hyperexcitAbility in TRPV1-expressing bronchopulmonAry C-fibers through the ActivAtion of protein kinAse C (PKC). Here, we hAve investigAted the PKC isoform responsible for this signAling. We found PKCβ1, PKCδ And PKCe were expressed by mAny vAgAl neurons, with PKCα And PKCβ2 expressed by subsets of vAgAl neurons. In dissociAted vAgAl neurons, Antimycin A cAused trAnslocAtion of PKCα but not the other isoforms, And only in TRPV1-lineAge neurons. In bronchopulmonAry C-fiber recordings, Antimycin A increAsed the number of Action potentiAls evoked by α,β-methylene ATP. Selective inhibition of PKCα, PKCβ1 And PKCβ2 with 50 nM bisindolylmAleimide I prevented the Antimycin-induced bronchopulmonAry C-fiber hyperexcitAbility, whereAs selective inhibition of only PKCβ1 And PKCβ2 with 50 nM LY333531 hAd no effect. We therefore conclude thAt PKCα is required for Antimycin-induced increAses in bronchopulmonAry C-fiber excitAbility.
-
Antimycin A induced mitochondriAl dysfunction ActivAtes vAgAl sensory neurons viA ros dependent ActivAtion of trpA1 And ros independent ActivAtion of trpv1
Brain Research, 2019Co-Authors: Katherine R Stanford, Stephen H Hadley, Parmvir K Bahia, Ivan Barannikov, Joanne M Ajmo, Thomas E TaylorclarkAbstract:AbstrAct InflAmmAtion cAuses ActivAtion of nociceptive sensory nerves, resulting in debilitAting sensAtions And reflexes. InflAmmAtion Also induces mitochondriAl dysfunction through multiple mechAnisms. Sensory nerve terminAls Are densely pAcked with mitochondriA, suggesting thAt mitochondriAl signAling mAy plAy A role in inflAmmAtion-induced nociception. We hAve previously shown thAt Agents thAt induce mitochondriAl dysfunction, such As Antimycin A, ActivAte A subset of nociceptive vAgAl sensory nerves thAt express trAnsient receptor potentiAl (TRP) chAnnels Ankyrin 1 (A1) And vAnilloid 1 (V1). However, the mechAnisms underlying these responses Are incompletely understood. Here, we studied the contribution of TRPA1, TRPV1 And reActive oxygen species (ROS) to Antimycin A-induced vAgAl sensory nerve ActivAtion in dissociAted neurons And At the sensory terminAls of bronchopulmonAry C-fibers. Nociceptive neurons were defined chemicAlly And geneticAlly. Antimycin A-evoked ActivAtion of vAgAl nociceptors in A FurA2 CA2+ AssAy correlAted with TRPV1 responses compAred to TRPA1 responses. Nociceptor ActivAtion wAs dependent on both TRP chAnnels, with TRPV1 predominAting in A mAjority of responding nociceptors And TRPA1 predominAting only in nociceptors with the greAtest responses. Surprisingly, both TRPA1 And TRPV1 were ActivAted by H2O2 when expressed in HEK293. Nevertheless, tArgeting ROS hAd no effect of Antimycin A-evoked TRPV1 ActivAtion in either HEK293 or vAgAl neurons. In contrAst, tArgeting ROS inhibited Antimycin A-evoked TRPA1 ActivAtion in HEK293, vAgAl neurons And bronchopulmonAry C-fibers, And A ROS-insensitive TRPA1 mutAnt wAs completely insensitive to Antimycin A. We therefore conclude thAt mitochondriAl dysfunction ActivAtes vAgAl nociceptors by ROS-dependent (TRPA1) And ROS-independent (TRPV1) mechAnisms.
Ivan Barannikov - One of the best experts on this subject based on the ideXlab platform.
-
Antimycin A increAses bronchopulmonAry c fiber excitAbility viA protein kinAse c AlphA
Respiratory Physiology & Neurobiology, 2020Co-Authors: Parmvir K Bahia, Stephen H Hadley, Ivan Barannikov, Isobel Sowells, Seolhee Kim, Thomas E TaylorclarkAbstract:InflAmmAtion cAn increAse the excitAbility of bronchopulmonAry C-fibers leAding to excessive sensAtions And reflexes (e.g. wheeze And cough). We hAve previously shown modulAtion of peripherAl nerve terminAl mitochondriA by Antimycin A cAuses hyperexcitAbility in TRPV1-expressing bronchopulmonAry C-fibers through the ActivAtion of protein kinAse C (PKC). Here, we hAve investigAted the PKC isoform responsible for this signAling. We found PKCβ1, PKCδ And PKCe were expressed by mAny vAgAl neurons, with PKCα And PKCβ2 expressed by subsets of vAgAl neurons. In dissociAted vAgAl neurons, Antimycin A cAused trAnslocAtion of PKCα but not the other isoforms, And only in TRPV1-lineAge neurons. In bronchopulmonAry C-fiber recordings, Antimycin A increAsed the number of Action potentiAls evoked by α,β-methylene ATP. Selective inhibition of PKCα, PKCβ1 And PKCβ2 with 50 nM bisindolylmAleimide I prevented the Antimycin-induced bronchopulmonAry C-fiber hyperexcitAbility, whereAs selective inhibition of only PKCβ1 And PKCβ2 with 50 nM LY333531 hAd no effect. We therefore conclude thAt PKCα is required for Antimycin-induced increAses in bronchopulmonAry C-fiber excitAbility.
-
Antimycin A induced mitochondriAl dysfunction ActivAtes vAgAl sensory neurons viA ros dependent ActivAtion of trpA1 And ros independent ActivAtion of trpv1
Brain Research, 2019Co-Authors: Katherine R Stanford, Stephen H Hadley, Parmvir K Bahia, Ivan Barannikov, Joanne M Ajmo, Thomas E TaylorclarkAbstract:AbstrAct InflAmmAtion cAuses ActivAtion of nociceptive sensory nerves, resulting in debilitAting sensAtions And reflexes. InflAmmAtion Also induces mitochondriAl dysfunction through multiple mechAnisms. Sensory nerve terminAls Are densely pAcked with mitochondriA, suggesting thAt mitochondriAl signAling mAy plAy A role in inflAmmAtion-induced nociception. We hAve previously shown thAt Agents thAt induce mitochondriAl dysfunction, such As Antimycin A, ActivAte A subset of nociceptive vAgAl sensory nerves thAt express trAnsient receptor potentiAl (TRP) chAnnels Ankyrin 1 (A1) And vAnilloid 1 (V1). However, the mechAnisms underlying these responses Are incompletely understood. Here, we studied the contribution of TRPA1, TRPV1 And reActive oxygen species (ROS) to Antimycin A-induced vAgAl sensory nerve ActivAtion in dissociAted neurons And At the sensory terminAls of bronchopulmonAry C-fibers. Nociceptive neurons were defined chemicAlly And geneticAlly. Antimycin A-evoked ActivAtion of vAgAl nociceptors in A FurA2 CA2+ AssAy correlAted with TRPV1 responses compAred to TRPA1 responses. Nociceptor ActivAtion wAs dependent on both TRP chAnnels, with TRPV1 predominAting in A mAjority of responding nociceptors And TRPA1 predominAting only in nociceptors with the greAtest responses. Surprisingly, both TRPA1 And TRPV1 were ActivAted by H2O2 when expressed in HEK293. Nevertheless, tArgeting ROS hAd no effect of Antimycin A-evoked TRPV1 ActivAtion in either HEK293 or vAgAl neurons. In contrAst, tArgeting ROS inhibited Antimycin A-evoked TRPA1 ActivAtion in HEK293, vAgAl neurons And bronchopulmonAry C-fibers, And A ROS-insensitive TRPA1 mutAnt wAs completely insensitive to Antimycin A. We therefore conclude thAt mitochondriAl dysfunction ActivAtes vAgAl nociceptors by ROS-dependent (TRPA1) And ROS-independent (TRPV1) mechAnisms.