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Oxidatív stressz és sejthalál

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(1)

Oxidatív stressz és sejthalál

Lőrincz Tamás

BME-ABÉT

doktorjelölt

(2)

Néma lombok hullása - apoptózis

Átlagosan napi 5 – 8 x10^10 = minden 1000-ből 5

(3)

z-VAD-fmk

(4)

(72h, 937 cells) (~15 000)

(+TNFa +zVAD)

Nekroptózis

Degterev A, Huang Z, Boyce M, et al (2005)

Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.

Nat Chem Biol 1:112–119.

(5)

Degterev A, Huang Z, Boyce M, et al (2005)

Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury.

Nat Chem Biol 1:112–119.

(L929, 36h)

(FADD-)

(BALB/c 3T3 cells)

(6)

Autofágia mechaniumusa

(7)

Cho YS, Challa S, Moquin D, et al (2009)

Phosphorylation-Driven Assembly of the RIP1-RIP3 Complex Regulates Programmed Necrosis and Virus- Induced Inflammation.

Cell 137:1112–1123. doi: 10.1016/j.cell.2009.05.037

(8)

Retinaleválás által kiváltott fotoreceptor nekrózis

Trichonas G, Murakami Y, Thanos A, et al (2010)

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis.

Proc Natl Acad Sci 107:21695–21700

(9)

Retinaleválás által kiváltott fotoreceptor nekrózis

Trichonas G, Murakami Y, Thanos A, et al (2010)

Receptor interacting protein kinases mediate retinal detachment-induced photoreceptor necrosis and compensate for inhibition of apoptosis.

Proc Natl Acad Sci 107:21695–21700

(10)

MLKL, necrosulfonamide

Sun L, Wang H, Wang Z, et al (2012)

Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.

Cell 148:213–227. doi: 10.1016/j.cell.2011.11.031

(11)

MLKL, necrosulfonamide

Sun L, Wang H, Wang Z, et al (2012)

Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.

Cell 148:213–227. doi: 10.1016/j.cell.2011.11.031 RIP3 punctae,

de kisebbek mint NSA nélkül

Fokozott RIP1/3-P

(12)

MLKL, necrosulfonamide

Sun L, Wang H, Wang Z, et al (2012)

Mixed lineage kinase domain-like protein mediates necrosis signaling downstream of RIP3 kinase.

Cell 148:213–227. doi: 10.1016/j.cell.2011.11.031

(13)

Genotípus-szelektív antitumor ágensek

Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003)

Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.

Cancer Cell 3:285–296.

23 550 vegyület, ebből 20 000 kombinatorikus

(14)

Genotípus-szelektív antitumor ágensek

Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003)

Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.

Cancer Cell 3:285–296.

(15)

Genotípus-szelektív antitumor ágensek

Dolma S, Lessnick SL, Hahn WC, Stockwell BR (2003)

Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells.

Cancer Cell 3:285–296.

(16)

Genotípus-szelektív antitumor ágensek

Yang WS, Stockwell BR (2008)

Synthetic Lethal Screening Identifies Compounds Activating Iron-Dependent, Nonapoptotic Cell Death in Oncogenic-RAS-Harboring

Cancer Cells. Chem Biol 15:234–245.

(17)

Genotípus-szelektív antitumor ágensek

Yang WS, Stockwell BR (2008)

Synthetic Lethal Screening Identifies Compounds Activating Iron-Dependent, Nonapoptotic Cell Death in Oncogenic-RAS-Harboring

Cancer Cells. Chem Biol 15:234–245.

(18)

Ferroptózis

Dixon SJ, Lemberg KM, Lamprecht MR, et al (2012)

Ferroptosis: An iron-dependent form of nonapoptotic cell death.

Cell 149:1060–1072. doi: 10.1016/j.cell.2012.03.042

2h 4h 6h

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Ferroptózis

Dixon SJ, Lemberg KM, Lamprecht MR, et al (2012)

Ferroptosis: An iron-dependent form of nonapoptotic cell death.

Cell 149:1060–1072. doi: 10.1016/j.cell.2012.03.042

(21)

Ferroptózis

Dixon SJ, Lemberg KM, Lamprecht MR, et al (2012)

Ferroptosis: An iron-dependent form of nonapoptotic cell death.

Cell 149:1060–1072. doi: 10.1016/j.cell.2012.03.042

(22)

Ferroptózis – autofágia ?

Gao M, Monian P, Pan Q, et al (2016)

Ferroptosis is an autophagic cell death process.

Cell Res 26:1021–32. doi: 10.1038/cr.2016.95

(23)

Autofágia mechaniumusa

(24)

Ferroptózis – autofágia ?

Gao M, Monian P, Pan Q, et al (2016)

Ferroptosis is an autophagic cell death process.

Cell Res 26:1021–32. doi: 10.1038/cr.2016.95

(25)

Ferroptózis – autofágia ?

Gao M, Monian P, Pan Q, et al (2016)

Ferroptosis is an autophagic cell death process.

Cell Res 26:1021–32. doi: 10.1038/cr.2016.95

(26)

Ferroptózis – autofágia ?

Gao M, Monian P, Pan Q, et al (2016)

Ferroptosis is an autophagic cell death process.

Cell Res 26:1021–32. doi: 10.1038/cr.2016.95

(27)

Ferroptózis (?)

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