• Shengnan Wu, Da Xing, Xuejuan Gao, and Wei R Chen.
• MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, Guangzhou, China.
• J. Cell. Physiol. 2009 Mar 1; 218 (3): 603-11.

AbstractHigh fluence low-power laser irradiation (HF-LPLI) can induce cell apoptosis via the mitochondria/caspase-3 pathway. Here, we further investigated the mechanism involved in the apoptotic process in human lung adenocarcinoma cells (ASTC-a-1) at a laser irradiation fluence of 120 J/cm(2) (633 nm). Cytochrome c release was ascribed to mitochondrial permeability transition (MPT) because the release was prevented by cyclosporine (CsA), a specific inhibitor of MPT. Furthermore, mitochondrial permeability for calcein (approximately 620 Da) was another evidence for the MPT induction under HF-LPLI treatment. A high-level intracellular reactive oxygen species (ROS) generation was observed after irradiation. The photodynamically produced ROS caused onset of MPT, as the ROS scavenger docosahexaenoic acid (DHA) prevented the MPT. However, CsA failed to prevented cell death induced by HF-LPLI, indicating the existence of other signaling pathways. Following laser irradiation, Bax activation occurred after mitochondrial depolarization and cytochrome c release, indicating Bax activation was a downstream event. In the presence of CsA, Bax was still activated at the end-stage of apoptotic process caused by HF-LPLI, suggesting that Bax was involved in an alternative-signaling pathway, which was independent of MPT. Under HF-LPLI treatment, cell viabilities due to pre-treatment with DHA, CsA, or Bax small interfering RNA (siRNA) demonstrated that the MPT signaling pathway was dominant, while Bax signaling pathway was secondary, and more importantly ROS mediated both pathways. Taken together, these results showed that HF-LPLI induced cell apoptosis via the CsA-sensitive MPT, which was ROS-dependent. Furthermore, there existed a secondary signaling pathway through Bax activation. The observed link between MPT and triggering ROS could be a fundamental phenomenon in HF-LPLI-induced cell apoptosis.

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