UV irradiation/cold shock-mediated apoptosis is switched to bubbling cell death at low temperatures

Szu Jung Chen, Pei Wen Lin, Hsin Ping Lin, Shenq Shyang Huang, Feng Jie Lai, Hamm Ming Sheu, Li Jin Hsu, Nan Shan Chang

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)


When COS7 fibroblasts and other cells were exposed to UVC irradiation and cold shock at 4°C for 5 min, rapid upregulation and nuclear accumulation of NOS2, p53, WWOX, and TRAF2 occurred in 10-30 min. By time-lapse microscopy, an enlarging gas bubble containing nitric oxide (NO) was formed in the nucleus in each cell that finally popped out to cause "bubbling death". Bubbling occurred effectively at 4 and 22°C, whereas DNA fragmentation was markedly blocked at 4°C. When temperature was increased to 37°C, bubbling was retarded and DNA fragmentation occurred in 1 hr, suggesting that bubbling death is switched to apoptosis with increasing temperatures. Bubbling occurred prior to nuclear uptake of propidium iodide and DAPI stains. Arginine analog Nω-LAME inhibited NO synthase NOS2 and significantly suppressed the bubbling death. Unlike apoptosis, there were no caspase activation and flip-over of membrane phosphatidylserine (PS) during bubbling death. Bubbling death was significantly retarded in Wwox knockout MEF cells, as well as in cells overexpressing TRAF2 and dominant-negative p53. Together, UV/cold shock induces bubbling death at 4°C and the event is switched to apoptosis at 37°C. Presumably, proapoptotic WWOX and p53 block the protective TRAF2 to execute the bubbling death.

Original languageEnglish
Pages (from-to)8007-8018
Number of pages12
Issue number10
Publication statusPublished - 2015

All Science Journal Classification (ASJC) codes

  • Oncology


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