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Nucleus Near-Infrared (nNIR) Irradiation of Single A549 Cells Induces DNA Damage and Activates EGFR Leading to Mitochondrial Fission

為了解決KREAM的問題，作者MOMOH GBETUWA 這樣論述：

Abstract Background: There has been great interest in identifying the biological substrate for light-cell interaction and their relations to cancer treatment. In our study, a single cell nuclear NIR (nNIR) and cytosol exposed NIR has been used to determine for the first-time mitochondria fragmentat

ion count (MFC) to compare NIR effect on subcellular cells. Near infra-red (NIR) possesses less light scattering and absorption in biological tissues it has a biological window that bears a very small photodamage and thus possesses a deep tissue penetration depth. Aim: To evaluate near-infrared (NIR

) laser focused into the nucleus (nNIR) or cytoplasm (cNIR) of a single living cell by a high numerical aperture condenser to dissect the novel role of cell nucleus in mediating NIR effects on mitochondrial dynamics of A549 non-small cell lung cancer cells.Materials and Methods: Cultured 150 single

cell of A549 nucleus and cytosol were incubated with 0.3 μM mitotracker green for 30 min washed with PBS, imaged control cell then treated with 224.02 J/cm2 NIR for 10 s and cells imaged at different time points of 1, 5, 10, 15 and 20 min. A549 cells were treated with conjugated 100 nM FND-EGF and i

ncubated with PD153035, caffeine and cetuximab for 1 h, and imaged cells. Results: Our analysis showed nNIR, but not cNIR, triggered mitochondrial fission in 10 minutes. On the contrast, the fission/fusion balance of mitochondria directly exposed to cNIR does not change. While the same phenomenon is

also triggered by single molecular interactions between epidermal growth factor (EGF) and its receptor EGFR, pharmacological studies with cetuximab, PD153035 and caffeine suggest EGF signaling crosstalk to DNA damaging response to mediate rapid mitochondrial fission as a result of nNIR irradiation.

These results suggest that nuclear DNA integrity is a novel biological target for cellular response to NIR. Conclusions: These results suggest that nuclear DNA integrity is a novel biological target for cellular response to NIR. Keywords: Keywords: near infrared (NIR), epidermal growth factor recep

tor (EGFR), mitochondrial fragmentation count (MFC), mitochondrial dynamic, cetuximab, caffeine.