masterThesis
Proteômica comparativa de linhagens celulares humanas expostas a estresse oxidativo induzido por riboflavina fotossensibilizada
Fecha
2011-09-28Registro en:
TIMOTEO, Ana Rafaela de Souza. Proteômica comparativa de linhagens celulares humanas expostas a estresse oxidativo induzido por riboflavina fotossensibilizada. 2011. 77 f. Dissertação (Mestrado em Biodiversidade; Biologia Estrutural e Funcional.) - Universidade Federal do Rio Grande do Norte, Natal, 2011.
Autor
Timoteo, Ana Rafaela de Souza
Resumen
Reactive oxygen species (ROS) are continuously generated and can be
derived from cellular metabolism or induced by exogenous factors, in addition, have
the capacity to damage molecules like DNA and proteins. BER is considered the
main route of DNA damage oxidative repair, however, several studies have
demonstrated the importance of the proteins participation of other ways to correct
these injuries. NER enzymes deficiency, such as CSB and XPC, acting in the
damage recognition step in the two subways this system influences the effectiveness
of oxidative damage repair. However, the mechanisms by which cells deficient in
these enzymes respond to oxidative stress and its consequences still need to be
better understood. Thus, the aim of this study was to perform a proteomic analysis of
cell lines proficient and deficient in NER, exposed to oxidative stress, in order to
identify proteins involved, directly or not, in response to oxidative stress and DNA
repair. For this, three strains of human fibroblasts, MRC5-SV, CS1AN (CSBdeficient)
and XP4PA (XPC-deficient) were treated with photosensitized riboflavin
and then carried out the differentially expressed proteins identification by mass
spectrometry. From the results, it was observed in MRC5-SV increase expression in
most of the proteins involved in cellular defense, an expected response to a normal
cell line subjected to stress. CS1AN showed a response disjointed, it is not possible
to establish many interactions between the proteins identified, may be one
explanation for their sensitivity to treatment with riboflavin and other oxidants and
increased cell death probably by induction of pro-apoptotic pathways. Already
XP4PA showed higher expression of apoptosis-blocking proteins, as there was
inhibition or reduced expression of others involved with the activation of this process,
suggesting the activation of an anti-apoptotic mechanism in this lineage, which may
help explain the high susceptibility to develop cancers in XPC individuals. These
results also contribute to elucidate action mechanisms of NER in oxidative damage
and the understanding of important routes in the oxidative stress correlation, repair
and malignant tumors formation