Low temperature protects mammalian cells from apoptosis initiated by various stimuli in vitro

Journal Article · Sat Oct 01 04:00:00 EDT 2005 · Experimental Cell Research

DOI:https://doi.org/10.1016/j.yexcr.2005.06.002· OSTI ID:20717659

Sakurai, Toshiharu ^[1]; Itoh, Katsuhiko ^[1]; Yu, Liu ^[1]; Higashitsuji, Hiroaki ^[1]; Sumitomo, Yasuhiko ^[1]; Sakamaki, Kazuhiro ^[2]; Fujita, Jun ^[1]

---

1. Department of Clinical Molecular Biology, Graduate School of Medicine, Kyoto University, 54 Shogoin Kawaharacho, Sakyo-ku, Kyoto 606-8507 (Japan)
2. Graduate School of Biostudies, Kyoto University, Kyoto (Japan)

Mild hypothermia shows protective effects on patients with brain damage and cardiac arrest. To elucidate the molecular mechanisms underlying these effects, we examined the effects of low temperature (32 deg. C) on cells exposed to a variety of stress in vitro. We found that 32 deg. C suppressed induction of apoptosis by cytotoxic stimuli such as adriamycin, etoposide, thapsigargin, NaCl, H{sub 2}O{sub 2}, and anti-Fas antibody. In adriamycin-treated BALB/3T3 cells, the down-shift in temperature from 37 deg. C to 32 deg. C increased the Bcl-xL protein level and decreased the mRNA level of Puma and mitochondrial translocation of Bax, suppressing caspase-9-mediated apoptosis. Furthermore, the protein level and stability of p53 were decreased, and its nuclear export was increased concomitant with Mdm2 mRNA upregulation. The low temperature effect was not observed in p53 {sup -/-}/Mdm2 {sup -/-} mouse embryonic fibroblasts, suggesting that the effect is mediated by suppression of the p53 pathway. In contrast, while thapsigargin-induced apoptosis was suppressed by the low temperature, no effect on the p53 protein level was observed. Furthermore, the survival rate of p53 {sup -/-}/Mdm2 {sup -/-} cells exposed to thapsigargin was increased when cultured at 32 deg. C compared with 37 deg. C. In conclusion, mild hypothermia protects cells from a variety of stress by p53-dependent and p53-independent mechanisms.

• OSTI ID: 20717659
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 2 Vol. 309; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
APOPTOSIS
BIOLOGICAL STRESS
BRAIN
DEATH
DNA DAMAGES
DOXORUBICIN
ENDOPLASMIC RETICULUM
FIBROBLASTS
HYDROGEN PEROXIDE
HYPOTHERMIA
IN VITRO
INHIBITION
MICE
PATIENTS
RECEPTORS
STIMULI
TRANSLOCATION