Stavrosporin sproži apoptozo in nekroptozo v kulturi astrocitov podgan

doktorska disertacija

Janez Šimenc (Author), Metoda Lipnik-Štangelj (Mentor), Ivan Krajnc (Thesis defence commission member)

Abstract

Apoptoza in nekroptoza sta dve različni obliki programirane celične smrti. Apoptoza je nujna za tkivno homeostazo, nekroptoza pa lahko povzroči obsežno izgubo celic in sproži lokalno vnetje. Astrociti so heterogena skupina celic v osrednjem živčnem sistemu, ki nudi razvojno in zaščitno podporo nevronom. Astrociti lahko umrejo z apoptozo ali nekroptozo, vendar so mehanizmi njihovega propadanja slabo znani. V naši študiji smo pokazali, da lahko stavrosporin sproži v konfluentni kulturi astrocitov podgan apoptozo ali nekroptozo. Pri tretiranju z 10-7 M stavrosporinom je bil delež apoptotičnih celic po regeneraciji v mediju brez stavrosporina značilno povečan. Pri inhibiciji kaspaz je bila apoptoza oslabljena, hkrati pa je bila nekroptoza povišana. Pri tretiranju z 10-6 M stavrosporinom in regeneraciji, pa je bila povečana nekroptoza. Nekroptozo je oslabil nekrostatin-1, specifični inhibitor kinaze RIP1. Aktivacija kinaze RIP1 s stavrosporinom je sprožila tudi povečano tvorbo kisikovih radikalov. Ugotovili smo tudi, da apoptoza poteka počasneje od nekroptoze.

Keywords

zastrupitve;odmiranje;celična smrt;pretočna citometrija;astrociti;

Data

Language:	Slovenian
Year of publishing:	2012
Typology:	2.08 - Doctoral Dissertation
Organization:	UM MF - Faculty of Medicine
Publisher:	J. Šimenc]
UDC:	577.1(043.3)
COBISS:	512244536
Views:	2805
Downloads:	167
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	Staurosporine induces apoptosis and necroptosis in cultured rat astrocytes
Secondary abstract:	Apoptosis and necroptosis are two different forms of a programmed cell death. Necroptosis may cause significant cell loss and local inflammation, while apoptosis is necesseary for tissue homeostasis. Astrocytes are heterogeneous cell population in the central nervous system, with many supportive and developmental functions to neurons. Astrocytes may die by apoptosis or necroptosis; however their demise is still poorly understood. In this study, we showed, that staurosporine in cultured rat astrocytes is able to induce both, apoptosis and necroptosis. Treatment with 10-7 M staurosporine increased apoptosis of astrocytes after the regeneration. When caspases were inhibited, apoptosis was attenuated, while necroptosis was slightly increased. However, treatment with 10-6 M staurosporine induced necroptosis. Necroptosis was significantly attenuated by necrostatin-1, an inhibitor of RIP1 kinase. Also, RIP1 kinase increased the production of reactive oxygen species. We also found, that apoptosis is much slower than necroptosis.
Secondary keywords:	Staurosporine;apoptosis;necroptosis;astrocytes;flow cytometry;
URN:	URN:SI:UM:
Type (COBISS):	Dissertation
Thesis comment:	Univ. v Mariboru, Medicinska fak.
Pages:	89 f.
ID:	8725799