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

Chen SJ, Lin PW, Lin HP, Huang SS, Lai FJ, Sheu HM, Hsu LJ, Chang NS - Oncotarget (2015)

Bottom Line: Arginine analog Nω-LAME inhibited NO synthase NOS2 and significantly suppressed the bubbling death.Bubbling death was significantly retarded in Wwox knockout MEF cells, as well as in cells overexpressing TRAF2 and dominant-negative p53.Presumably, proapoptotic WWOX and p53 block the protective TRAF2 to execute the bubbling death.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Electron microscopy of UV/cold shock-induced gas formation to cause damage to the nucleusCOS7 cells were exposed to UV irradiation (480 mJoule/cm2) and then incubated at 4°C for 3 hours. Cells were fixed and prepared for electron microscopy analysis. (A–B) COS7 cells were without treatment. Intact nuclear pores are shown (see arrows). (C–D) A single gas hit to the nuclear wall is shown, which results in burst of the nucleus with a single opening (red arrow).
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Figure 3: Electron microscopy of UV/cold shock-induced gas formation to cause damage to the nucleusCOS7 cells were exposed to UV irradiation (480 mJoule/cm2) and then incubated at 4°C for 3 hours. Cells were fixed and prepared for electron microscopy analysis. (A–B) COS7 cells were without treatment. Intact nuclear pores are shown (see arrows). (C–D) A single gas hit to the nuclear wall is shown, which results in burst of the nucleus with a single opening (red arrow).

Mentions: Finally, we attempted to verify the gas one-hit theory that a gas jet stream is formed in the nucleus and pops off to form one bubble per cell. COS7 cells were subjected to UV/cold shock, and then fixed for electron microscopy analysis [17]. In controls, COS7 cells received no UV/cold shock and their nuclei and nuclear pores were intact (see red arrows; Figure 3A–3B). When cells were subjected to UV/cold shock, a representative damaged nucleus underwent condensation and possessed an enlarged burst of the nuclear membrane (see the red arrow; Figure 3C–3D), suggesting that a gas jet stream hits the nuclear wall or pushes apart of a single nuclear pore that results in nuclear burst.


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

Chen SJ, Lin PW, Lin HP, Huang SS, Lai FJ, Sheu HM, Hsu LJ, Chang NS - Oncotarget (2015)

Electron microscopy of UV/cold shock-induced gas formation to cause damage to the nucleusCOS7 cells were exposed to UV irradiation (480 mJoule/cm2) and then incubated at 4°C for 3 hours. Cells were fixed and prepared for electron microscopy analysis. (A–B) COS7 cells were without treatment. Intact nuclear pores are shown (see arrows). (C–D) A single gas hit to the nuclear wall is shown, which results in burst of the nucleus with a single opening (red arrow).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4480731&req=5

Figure 3: Electron microscopy of UV/cold shock-induced gas formation to cause damage to the nucleusCOS7 cells were exposed to UV irradiation (480 mJoule/cm2) and then incubated at 4°C for 3 hours. Cells were fixed and prepared for electron microscopy analysis. (A–B) COS7 cells were without treatment. Intact nuclear pores are shown (see arrows). (C–D) A single gas hit to the nuclear wall is shown, which results in burst of the nucleus with a single opening (red arrow).
Mentions: Finally, we attempted to verify the gas one-hit theory that a gas jet stream is formed in the nucleus and pops off to form one bubble per cell. COS7 cells were subjected to UV/cold shock, and then fixed for electron microscopy analysis [17]. In controls, COS7 cells received no UV/cold shock and their nuclei and nuclear pores were intact (see red arrows; Figure 3A–3B). When cells were subjected to UV/cold shock, a representative damaged nucleus underwent condensation and possessed an enlarged burst of the nuclear membrane (see the red arrow; Figure 3C–3D), suggesting that a gas jet stream hits the nuclear wall or pushes apart of a single nuclear pore that results in nuclear burst.

Bottom Line: Arginine analog Nω-LAME inhibited NO synthase NOS2 and significantly suppressed the bubbling death.Bubbling death was significantly retarded in Wwox knockout MEF cells, as well as in cells overexpressing TRAF2 and dominant-negative p53.Presumably, proapoptotic WWOX and p53 block the protective TRAF2 to execute the bubbling death.

View Article: PubMed Central - PubMed

Affiliation: Institute of Molecular Medicine, National Cheng Kung University College of Medicine, Tainan, Taiwan, ROC.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus