Glycogen synthase kinase-3β (GSK-3β) is a critical activator of cell apoptosis induced by a diverse array of insults.
However, the effects of GSK-3β on the human lung adenocarcinoma cell (ASTC-a-1) apoptosis induced by high fluence
low-power laser irradiation (HF-LPLI) are not clear. Here, we showed that GSK-3β was constantly translocated from
cytoplasm to nucleus and activated during HF-LPLI-induced cell apoptosis. In addition, we found that co-overexpression
of YFP-GSK-3β and CFP-Bax in ASTC-a-1 cells accelerated both Bax translocations to mitochondria and cell apoptosis,
compared to the cells expressed CFP-Bax only under HF-LPLI treatment, indicating that GSK-3β facilitated ASTC-a-1
cells apoptosis through acceleration mitochondrial translocation of Bax. Our results demonstrate that GSK-3β exerts
some of its pro-apoptotic effects in ASTC-a-1 cells by regulating the mitochondrial localization of Bax, a key component
of the intrinsic apoptotic cascade.
Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and
longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of
SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present
studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green
monkey SV40-transformed kidney fibroblast cells (COS-7). Using
SIRT1-EGFP fluorescence reporter, we found that
SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor
deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of
SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation,
because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together,
we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible
connection between cytoplasm-localized SIRT1 and the aging process.
Mitochondrial injury, characterized by its depolarization, is a key to cell apoptosis. High fluence low-power laser
irradiation (HF-LPLI) through endogenous photosensitive reactions can cause mitochondrial injury. However, the exact
mechanisms are not fully understood. Using fluorescent image techniques, we investigated cell apoptosis caused by
mitochondrial photosensitization by HF-LPLI. Our results showed that the major step of the apoptosis, decrease of
mitochondrial transmembrane potential (ΔΨm), occurred accompanying with high levels of mitochondrial reactive
oxygen species (ROS) generation, indicating mitochondrial injury caused by ROS. Scavenging the photodynamical
ROS completely prevented mitochondrial depolarization supported the view. Taken together, we demonstrated that
HF-LPLI caused mitochondrial injury through a large amount of mitochondrial ROS generation. The specific
mechanisms need to be further studied.
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