The extrinsic and intrinsic apoptotic pathways are differentially affected by temperature upstream of mitochondrial damage

Abstract

It is well known that mild hypothermia prevents neuronal cell death following cerebral ischemia, although it can also cause apoptosis in other cell types. Thus, incubation at room temperature (RT) has been shown to induce apoptosis in hematopoietic cells, including Jurkat T leukemia cells. To further understand the apoptotic events that can be activated at RT, we compared the induction of apoptosis by several apoptotic insults in Jurkat cells stimulated at 37 degrees C or RT. Retinoid-related molecules, which induce apoptosis via the intrinsic pathway, failed to induce apoptosis when cells were treated at RT, as determined by various apoptotic parameters including cytochrome c release and activation of caspase 3. In contrast, most apoptotic events were enhanced by lower temperatures when cells were stimulated with anti-Fas antibody via the extrinsic pathway. Ultraviolet radiation produced partial effects at RT, correlating with its capacity to activate both pathways. Our results indicate that the core caspase machinery is operational under mild hypothermia conditions. Experiments using purified recombinant caspases and cell-free assays confirmed that caspases are fully functional at RT. Other hallmark events of apoptosis, such as phosphatidylserine externalization and formation of apoptotic bodies were variably affected by RT in a stimulus-dependent manner, suggesting the existence of critical steps that are sensitive to temperature. Thus, analysis of apoptosis at RT might be useful to (i) discriminate between the extrinsic and intrinsic pathways in Jurkat cells treated with prospective stimuli, and (ii) to unravel temperature-sensitive steps of apoptotic signaling cascades.

Therapeutic Hypothermia: Critical Review of the Molecular Mechanisms of Action

“…Experimental models have shown that TH strongly inhibits the caspases pathway preventing apoptosis. The effect of hypothermia in theses pathways is such that makes it probably the therapeutic measure with the most benefit preventing neuronal apoptosis (Zhao et al, 2004; López-Hernández et al, 2006; Schmitt et al, 2007). …”

Apoptotic volume decrease as a geometric determinant for cell dismantling into apoptotic bodies

“…The whole process of apoptotic execution is active at room temperature (RT; 19-251C), including membrane blebbing, except apoptotic body release. 27 Because caspases are normally active at RT, 27 there is a caspase-independent, temperaturedependent step in the process of apoptotic body release, which remains to be determined.…”

Tumstatin induces apoptosis mediated by Fas signaling pathway in oral squamous cell carcinoma SCC-VII cells

“…4C). Fas is a death domain-containing member of the tumor necrosis factor receptor superfamily that plays a central role in the physiological regulation of apoptosis (22). The Fas-mediated apoptosis pathway involves the activation of procaspases.…”