Difference between revisions of "Ballot 2010 Apoptosis"
Beno Marija (talk | contribs) |
|||
(8 intermediate revisions by 5 users not shown) | |||
Line 1: | Line 1: | ||
{{Publication | {{Publication | ||
|title=Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Nevière R, Marchetti P (2010) Inhibition of mitochondrial respiration mediates apoptosis induced by the anti-tumoral alkaloid lamellarin D. Apoptosis 15: 769- | |title=Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Nevière R, Marchetti P (2010) Inhibition of mitochondrial respiration mediates apoptosis induced by the anti-tumoral alkaloid lamellarin D. Apoptosis 15:769-81. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/20151196 PMID: 20151196] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/20151196 PMID: 20151196] | ||
|authors=Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Neviere R, Marchetti P | |authors=Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Neviere R, Marchetti P | ||
Line 6: | Line 6: | ||
|journal=Apoptosis | |journal=Apoptosis | ||
|abstract=Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against many different tumors. The pro-apoptotic function of Lam D has been attributed to its direct induction of mitochondrial permeability transition (MPT). This study was undertaken to explore the mechanisms through which Lam D promotes changes in mitochondrial function and as a result apoptosis. The use of eight Lam derivatives provides useful structure-apoptosis relationships. We demonstrate that Lam D and structural analogues induce apoptosis of cancer cells by acting directly on mitochondria inducing reduction of mitochondrial membrane potential, swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT, completely prevents mitochondrial signs of apoptosis. The drug decreases calcium uptake by mitochondria but not by microsomes indicating that Lam D-dependent permeability is specific to mitochondrial membranes. In addition, upon Lam D exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs in isolated mitochondria as well as in intact cells. Evaluation of the site of action of Lam D on the electron-transport chain revealed that the activity of respiratory chain complex III is reduced by a half. To determine whether Lam D could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we generated respiration-deficient cells (rho0) derived from human melanoma cells. In comparison to parental cells, rho0 cells are totally resistant to the induction of MPT-dependent apoptosis by Lam D. Our results indicate that functional mitochondria are required for Lam D-induced apoptosis. Inhibition of mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer cells induced by Lam-D. | |abstract=Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against many different tumors. The pro-apoptotic function of Lam D has been attributed to its direct induction of mitochondrial permeability transition (MPT). This study was undertaken to explore the mechanisms through which Lam D promotes changes in mitochondrial function and as a result apoptosis. The use of eight Lam derivatives provides useful structure-apoptosis relationships. We demonstrate that Lam D and structural analogues induce apoptosis of cancer cells by acting directly on mitochondria inducing reduction of mitochondrial membrane potential, swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT, completely prevents mitochondrial signs of apoptosis. The drug decreases calcium uptake by mitochondria but not by microsomes indicating that Lam D-dependent permeability is specific to mitochondrial membranes. In addition, upon Lam D exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs in isolated mitochondria as well as in intact cells. Evaluation of the site of action of Lam D on the electron-transport chain revealed that the activity of respiratory chain complex III is reduced by a half. To determine whether Lam D could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we generated respiration-deficient cells (rho0) derived from human melanoma cells. In comparison to parental cells, rho0 cells are totally resistant to the induction of MPT-dependent apoptosis by Lam D. Our results indicate that functional mitochondria are required for Lam D-induced apoptosis. Inhibition of mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer cells induced by Lam-D. | ||
|keywords=Cytotoxicity, | |keywords=Cytotoxicity, Pro-apoptotic Lamellarin D (Lam D), Mitochondrial permeability transition (MPT), Human melanoma cells, Respiration-deficient cells (rho0) | ||
|mipnetlab=FR Lille Neviere R | |mipnetlab=FR Lille Neviere R, FR Lille Vienne JC, FR Lille Lancel Steve | ||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration, Pharmacology;toxicology | |||
|organism=Human | |||
|preparations=Intact cells, Isolated mitochondria | |||
|enzymes=Complex III, Complex V;ATP synthase | |||
|injuries=Cell death | |||
|topics=Inhibitor, Substrate | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 11:49, 22 December 2020
Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Nevière R, Marchetti P (2010) Inhibition of mitochondrial respiration mediates apoptosis induced by the anti-tumoral alkaloid lamellarin D. Apoptosis 15:769-81. |
Ballot C, Kluza J, Lancel S, Martoriati A, Hassoun SM, Mortier L, Vienne JC, Briand G, Formstecher P, Bailly C, Neviere R, Marchetti P (2010) Apoptosis
Abstract: Lamellarin D (Lam D), a marine alkaloid, exhibits a potent cytotoxicity against many different tumors. The pro-apoptotic function of Lam D has been attributed to its direct induction of mitochondrial permeability transition (MPT). This study was undertaken to explore the mechanisms through which Lam D promotes changes in mitochondrial function and as a result apoptosis. The use of eight Lam derivatives provides useful structure-apoptosis relationships. We demonstrate that Lam D and structural analogues induce apoptosis of cancer cells by acting directly on mitochondria inducing reduction of mitochondrial membrane potential, swelling and cytochrome c release. Cyclosporin A, a well-known inhibitor of MPT, completely prevents mitochondrial signs of apoptosis. The drug decreases calcium uptake by mitochondria but not by microsomes indicating that Lam D-dependent permeability is specific to mitochondrial membranes. In addition, upon Lam D exposure, a rapid decline of mitochondrial respiration and ATP synthesis occurs in isolated mitochondria as well as in intact cells. Evaluation of the site of action of Lam D on the electron-transport chain revealed that the activity of respiratory chain complex III is reduced by a half. To determine whether Lam D could induce MPT-dependent apoptosis by inhibiting mitochondrial respiration, we generated respiration-deficient cells (rho0) derived from human melanoma cells. In comparison to parental cells, rho0 cells are totally resistant to the induction of MPT-dependent apoptosis by Lam D. Our results indicate that functional mitochondria are required for Lam D-induced apoptosis. Inhibition of mitochondrial respiration is responsible for MPT-dependent apoptosis of cancer cells induced by Lam-D. • Keywords: Cytotoxicity, Pro-apoptotic Lamellarin D (Lam D), Mitochondrial permeability transition (MPT), Human melanoma cells, Respiration-deficient cells (rho0)
• O2k-Network Lab: FR Lille Neviere R, FR Lille Vienne JC, FR Lille Lancel Steve
Labels: MiParea: Respiration, Pharmacology;toxicology
Stress:Cell death Organism: Human
Preparation: Intact cells, Isolated mitochondria Enzyme: Complex III, Complex V;ATP synthase Regulation: Inhibitor, Substrate
HRR: Oxygraph-2k