E-Locus - Institutional Repository of the University of Crete - Διερεύνηση του προστατευτικού ρόλου του μονοπατίου απόκρισης σε θερμικό σοκ έναντι του νεκρωτικού κυτταρικού θανάτου στο νηματώδη Caenorhabditis elegans

Home Διερεύνηση του προστατευτικού ρόλου του μονοπατίου απόκρισης σε θερμικό σοκ έναντι του νεκρωτικού κυτταρικού θανάτου στο νηματώδη Caenorhabditis elegans

Results - Details

[Add to Basket]

Identifier

000369268

Title

Διερεύνηση του προστατευτικού ρόλου του μονοπατίου απόκρισης σε θερμικό σοκ έναντι του νεκρωτικού κυτταρικού θανάτου στο νηματώδη Caenorhabditis elegans

Alternative Title

Study of the protective role of the heat shock response pathway against necrotic cell death in the nematode Caenorhabditis elegans

Author

Κούρτης, Νικόλαος

Thesis advisor

Ταβερναράκης, Νεκτάριος

Abstract

Necrotic cell death contributes to the pathogenesis of many neurodegenerative diseases and other pathological situations. However, the molecular mechanisms underlying necrosis are not fully understood. We find that activation of the heat shock response pathway by means of heat preconditioning strongly suppresses necrotic cell death triggered by extreme environmental conditions in a model of heat stroke in C. elegans. Heat preconditioning also ameliorates excitotoxic neuronal death as well as necrosis caused by hypoxia, in C. elegans. The heat shock response is a highly conserved gene expression program, which is engaged under conditions of stress and coordinates expression of specific genes that protect cells against various stressors. Removal of the heat shock factor 1 (HSF-1), the master transcription regulator which orchestrates the heat shock response, abolishes the protective effect of heat preconditioning. By contrast, overexpression of HSF-1 suppresses neurodegeneration. While screening for potential mediators of the protective effect of heat preconditioning, we found that the small heat shock protein HSP-16.1 is both necessary and sufficient for protection against necrosis. HSP-16.1 exerts its protective effect by modulating calcium release from the Golgi apparatus. Interestingly, the Golgi specific Ca²⁺ pump pmr-1 is required for heat preconditioning to elicit its protective effect. Loss of pmr-1 function abolishes the capacity of hsp-16.1 overexpression to protect against necrotic cell death. Our findings suggest that intervention strategies based on selective manipulation of the heat shock response may effectively counter excitotoxicity and neurodegeneration.

Language

Greek

Subject

Heat stroke

Necrosis

Neurodegeneration

Stress

Θερμοπληξία

Νέκρωση

Νευροεκφυλισμός

Στρες

Issue date