Small stress protein Hsp27 accumulation during dopamine-mediated differentiation of rat olfactory neurons counteracts apoptosis

Abstract

The small stress protein Hsp27 is expressed during mammalian neural development. We have analyzed the role of this protein in immortalized rat olfactory neuroblasts. In the presence of dopamine a fraction of these cells differentiate into neurons while the remaining cells undergo apoptosis. We report here that the dopamine induced differentiation and apoptosis are associated with a transient and specific accumulation of Hsp27. Moreover, transfection experiments have shown that Hsp27 overexpression drastically decreases the fraction of cells undergoing apoptosis. In contrast, reduction of the endogenous level of Hsp27 led to abortion of differentiation and, therefore, drastically increased the number of apoptotic cells. Furthermore, in the normal cell population we show that Hsp27 accumulation takes place only in differentiating cells that were not undergoing apoptosis. We therefore conclude that Hsp27 may represent a key protein that controls the decision of olfactory precursor cells to undergo either differentiation or cell death.

Regulation of Hsp27 expression and cell survival by the POU transcription factor Brn3a

“…6 Hsp27 is highly expressed in neuronal cells and is shown to protect against neuronal cell apoptosis. 7 Mehlen et al 8 reported an increase in Hsp27 expression and Hsp27-dependent protection against apoptosis during dopamine-induced, cAMP-dependent differentiation of rat olfactory neuroblasts. Since there are direct parallels between survival and differentiation in these two experimental systems, we hypothesised that Hsp27 may represent a downstream target of the Brn3a transcription factor during neuronal cell survival and differentiation.…”

Overexpression of murine small heat shock protein HSP25 interferes with chondrocyte differentiation and decreases cell adhesion

“…The group of Arrigo has proposed that HSP25 could play a role as a switch between cell differentiation and apoptosis. 27,28 In ES cells or olfactory neurons undergoing differentiation, a transient expression of HSP25 accompanies arrest of cell proliferation and entry into differentiation. When this increase is altered, more cells undergo apoptosis.…”

“…24 ± 26 Another role has been proposed by the laboratory of Dr. A-P Arrigo : it could act as a switch between differentiation and apoptosis as demonstrated during cell line differentiation in vitro. 27,28 This role has been correlated with reduced glutathione regeneration in response to stress. 29,30 But the cellular mechanism is not clearly identified yet for the action of HSP25 in the differential control of differentiation and apoptosis.…”

Inhibition of Heat Shock Protein 27–Mediated Resistance to DNA Damaging Agents by a Novel PKCδ-V5 Heptapeptide

“…Heat shock protein 27 (HSP27), a human form of small heat shock protein (in murine system, HSP25 is present and these two forms have homology of more than 90%), has been suggested to protect cells from apoptotic cell death triggered by hyperthermia, ionizing radiation, oxidative stress, Fas ligand, and cytotoxic drugs (10)(11)(12). Several mechanisms have been proposed to account for the HSP27-mediated apoptotic protection.…”