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Heat shock transcription factors regulate heat induced cell death in a rat histiocytoma

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Abstract

Heat shock response is associated with the synthesis of heat shock proteins (Hsps) which is strictly regulated by different members of heat shock transcription factors (HSFs). We previously reported that a rat histiocytoma, BC-8 failed to synthesize Hsps when subjected to typical heat shock conditions (42°C, 60 min). The lack of Hsp synthesis in these cells was due to a failure in HSF1 DNA binding activity. In the present study we report that BC-8 tumor cells when subjected to heat shock at higher temperature (43°C, 60 min) or incubation for longer time at 42°C, exhibited necrosis characteristics; however, under mild heat shock (42°C, 30 min) conditions cells showed activation of autophagy. Mild heat shock treatment induced proteolysis of HSF1, and under similar conditions we observed an increase in HSF2 expression followed by its enhanced DNA binding activity. Inhibiting HSF1 proteolysis by reversible proteasome inhibition failed to inhibit heat shock induced autophagy. Compromising HSF2 expression but not HSF1 resulted in the inhibition of autophagy, suggesting HSF2 dependent activation of autophagy. We are reporting for the first time that HSF2 is heat inducible and functions in heat shock induced autophagic cell death in BC-8 tumor cells.

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Abbreviations

[(Ca2+)i]:

intracellular calcium

DioC6(3):

3′,3′-dihexyloxacarbocyanine iodide

Hsc70:

heat shock cognate protein 70

Hsp:

heat shock protein

Hsp70:

heat shock protein 70

H2-DCFDA:

2′,7′-dichlorodihydrofluorescein diacetate

HSE:

heat shock element

HSF:

heat shock transcription factor

lamp2a:

lysosomal-associated membrane protein

MDC:

monodansylcadaverine

Rhod-2:

1-[2-Amino-5-(3-dimethylamino-6-dimethylammonio-9-xanthenyl) phenoxy]-2-(2-amino-5-methylphenoxy)ethane-N,N,N′,N′-tetracetic acid chloride

ROS:

reactive oxygen species

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Author notes

  1. Kolla V Prasad

    Present address: Institute for Animal Pathology Universität Bern, 3001, Bern, Switzerland

Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, Hyderabad, 500 007, India

    Kolla V Prasad, Aftab Taiyab, D Jyothi, Usha K Srinivas & Amere S Sreedhar

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  1. Kolla V Prasad
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  2. Aftab Taiyab
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  3. D Jyothi
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Correspondence to Amere S Sreedhar.

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Prasad, K.V., Taiyab, A., Jyothi, D. et al. Heat shock transcription factors regulate heat induced cell death in a rat histiocytoma. J Biosci 32, 585–593 (2007). https://doi.org/10.1007/s12038-007-0058-4

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