OPOMNIK: IJS KOLOKVIJ,ponedeljek, 24. 03. 2014; ob 12. uri; prof. dr. Guido Krömer

[Tanja Debevec]

Vabimo vas na 11. predavanje iz sklopa "Kolokviji na IJS" v letu 2013/14, ki bo v ponedeljek, 24. marca 2014, ob 12. uri v Veliki predavalnici Instituta »Jožef Stefan«  na Jamovi cesti 39 v Ljubljani. Napovednik predavanja najdete tudi na naslovu http://www.ijs.si/ijsw/Koledar_prireditev, posnetke preteklih predavanj pa na http://videolectures.net/kolokviji_ijs. 

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prof. dr. Guido Krömer

Université de Paris Descartes, Assistance Publique-Hopitaux de Paris, 

Institut National de la Santé et de la Recherche Médicale, Gustave Roussy Cancer Campus, Pariz, Francija

 

Celična smrt v patofiziologiji: neizogibna, izogibna ali zaželena 

Razen nekaj potencialno nesmrtnih spolnih celic (gamet), ki jih proizvaja naše telo, delimo umrljive (somatske) celice na dve vrsti – na tiste, ki neprenehno nastajajo ob delitvi zarodnih celic, in na tiste, ki se od rojstva ne obnavljajo ali pa v zelo majhni meri, kot so nevroni ali kardiomiociti. Prve so programirane, da umrejo in jih telo vse življenje nadomešča z novimi, druge pa morajo vztrajati do naše smrti. Pretirana celična smrt posebej v postmitotičnih tkivih vodi do degenerativnih stanj, medtem se v odsotnosti pravočasne smrti v obnavljajočih se tkivih pojavita hiperplazija in rak. Naš prvotni prispevek k razumevanju biologije celične smrti je slonel na odkritju, da je stanje, v katerem se nepovratno začne smrt, mogoče prepoznati po permeabilizaciji mitohondrijske membrane. To pojasnjuje, zakaj inhibicija proteaz in nukleaz, ki prispevajo k razgradnji celice po razpadu mitohondrija, ne more zagotoviti trajne zaščite celic. Pokazali smo tudi, da avtofagija ni samouničujoči proces, kot so sprva domnevali, temveč da je v resnici učinkovit mehanizem zaščite celic, ki lahko podaljša življenjsko dobo raznih živalskih vrst, ce ga induciramo na ravni celega organizma. Avtofagija prispeva k izogibu smrti celic in organizmov preko t.i. procesa hormeze, pri čemer se z izpostavitvijo nizkim dozam sicer toksične snovi sčasoma poveča odpornost celic ali organizma na poškodbe in smrt. Nedavno smo dokazali zmotnost dogme, da je apoptoza kot posebna oblika programirane ali regulirane celične smrti po definiciji neimunogena. Odkrili smo, da je glede na sprožilce in predsmrtni odziv na stres apoptoza lahko imunogena in da lahko vzbudi lastni imunski sistem organizma, pri čemer stimulira specifični odziv na antigene mrtvih celic. Več uspešnih zdravil proti raku, ki so ohranila številna življenja, sproži to posebej zaželeno imunogeno vrsto celične smrti in tako spremenijo tumorje v terapevtsko cepivo, ki (re)aktivira imunski odziv, značilen za posamezno vrsto raka. Pri tem procesu pa predstavlja sprožitev avtofagije enega od predsmrtnih dogodkov, ki vzpodbujajo imunogenost apoptotskih telesc.

Predavanje bo v angleščini.

Lepo vabljeni!

 

 

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We invite you to the 11th Institute colloquium in the academic year 2013/14. The colloquium will be held on Monday March 24, 2014 at 12 PM in the main Institute lecture hall, Jamova 39, Ljubljana. To read the abstract click  http://www.ijs.si/ijsw/Koledar_prireditev. Past colloquia are posted on  http://videolectures.net/kolokviji_ijs.

 

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prof. dr. Guido Krömer

Université de Paris Descartes, Assistance Publique-Hopitaux de Paris, 

Institut National de la Santé et de la Recherche Médicale, Gustave Roussy Cancer Campus, Pariz, Francija

 

Cell death in pathophysiology: inexorable, avoidable or desirable

 

Beyond the few potentially immortal gametes that our body produces, mortal (somatic) cells fall into two classes, those that are constantly renewed from proliferating stem cells, such as epithelial cells and leukocytes, and those that are not (or scarcely) renewed after birth, such as neurons or cardiomyocytes. While the former are programmed to undergo cell death and are replaced throughout life, the latter must endure until we expire. Excessive cell death, in particular in post-mitotic tissues, precipitates degenerative states, while the failure to timely execute death in renovating tissues contributes to hyperplasia and cancer. Our initial contribution to cell (death) biology consisted in the discovery that mitochondrial membrane permeabilization marks the inexorable point-of-no-return of lethal pathways, explaining why the inhibition of proteases and nucleases that contribute to cellular dismantling downstream of mitochondria cannot provide durable cytoprotection. We also demonstrated that autophagy is not a self-destructive pathway, as it had initially been thought, but rather a potent cytoprotective mechanism that, if induced on the whole-organism level, can increase the longevity of several animal species. Thus, autophagy contributes to the avoidance of the death of cells and organisms in the context of hormesis, the phenomenon whereby exposure to low, sublethal doses of an otherwise toxic agent subsequently increases resistance against damage and death. More recently, we invalidated the dogma that apoptosis, which is one particular modality of programmed or regulated cell death, is by definition a non-immunogenic cell death modality. We found that, depending on the upstream triggers and the premortem stress responses, apoptosis can be immunogenic and hence alert the innate immune system, instructing it to stimulate specific responses against dead-cell antigens. Several successful anticancer drugs that have saved millions of life-years induce this particularly ‘desirable’, immunogenic cell death type and hence convert cancers into a therapeutic vaccine that (re)activates tumor-specific immune responses. The induction of autophagy is one of the premortem events that favors the immunogenicity of apoptotic corpses.

 

 

We look forward to meeting you at the “Kolokvij na IJS”!

 

 

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