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Int. J. Mol. Sci. 2011, 12(2), 1041-1059; doi:10.3390/ijms12021041

Photodynamic Treatment Induces an Apoptotic Pathway Involving Calcium, Nitric Oxide, p53, p21-Activated Kinase 2, and c-Jun N-Terminal Kinase and Inactivates Survival Signal in Human Umbilical Vein Endothelial Cells

Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, Chung Li 32023, Taiwan
Received: 28 December 2010 / Revised: 25 January 2011 / Accepted: 2 February 2011 / Published: 7 February 2011
(This article belongs to the Section Biochemistry, Molecular Biology and Biophysics)
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Abstract

Photodynamic treatment (PDT) elicits a diverse range of cellular responses, including apoptosis. Previously, we showed that PDT stimulates caspase-3 activity, and subsequent cleavage and activation of p21-activated kinase 2 (PAK2) in human epidermal carcinoma A431 cells. In the current study, pretreatment with nitric oxide (NO) scavengers inhibited PDT-induced mitochondrial membrane potential (MMP) changes, activation of caspase-9, caspase-3, p21-activated protein kinase 2 (PAK2) and c-Jun N-terminal kinase (JNK), and gene expression of p53 and p21 involved in apoptotic signaling. Moreover, PAK2 activity was required for PDT-induced JNK activation and apoptosis. Inhibition of p53 mRNA expression using small interfering RNA (siRNA) additionally blocked activation of PAK2 and apoptosis induced by PDT. Importantly, our data also show that PDT triggers cell death via inactivation of ERK-mediated anti-apoptotic pathway. PDT triggers cell death via inactivation of the HSP90/multi-chaperone complex and subsequent degradation of Ras, further inhibiting anti-apoptotic processes, such as the Ras→ERK signal transduction pathway. Furthermore, we did not observe two-stage JNK activation for regulation of PAK2 activity in the PDT-induced apoptotic pathway in HUVECs, which was reported earlier in A431 cells. Based on the collective results, we have proposed a model for the PDT-triggered inactivation of the survival signal and apoptotic signaling cascade with Rose Bengal (RB), which sequentially involves singlet oxygen, Ca2+, NO, p53, caspase-9, caspase-3, PAK2, and JNK.
Keywords: PDT; apoptosis; calcium; NO PDT; apoptosis; calcium; NO
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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MDPI and ACS Style

Chan, W.-H. Photodynamic Treatment Induces an Apoptotic Pathway Involving Calcium, Nitric Oxide, p53, p21-Activated Kinase 2, and c-Jun N-Terminal Kinase and Inactivates Survival Signal in Human Umbilical Vein Endothelial Cells. Int. J. Mol. Sci. 2011, 12, 1041-1059.

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