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Biomedical subjects

Stephen D Hsu

Publications and source records attributed to Stephen D Hsu.

6 recordsLinked to original sources
PubMed2006

Ni(II) activates the Nrf2 signaling pathway in human monocytic cells.

Nickel is a component of biomedical alloys that is released during corrosion and causes inflammation in tissues by as yet unknown mechanisms. Recent data show that Ni(II) at concentrations of 10-50 microM amplifies lipopolysaccharide-triggered, NFkappaB-mediated cytokine secretion from monocytes. In the current study, we tested the hypothesis that Ni(II) amplifies cytokine secretion by activating the Nrf2 antioxidant pathway rather than by enhancing activity of the NFkappaB signaling pathway. Human THP1 monocytes were exposed to Ni(II) concentrations of 10-30 microM for 6-72 h, then immunoblots of whole-cell lysates or cytosolic and nuclear proteins were used to detect changes in Nrf2 or NFkappaB signaling. Our results show that Ni(II) increased (by 1-2 fold) whole-cell Nrf2 levels and nuclear translocation of Nrf2, and amplified lipopolysaccharide (LPS)-induction of Nrf2 (by 3-5 fold), but had no detectable effect on the initial activation or nuclear translocation of NFkappaB. Because Nrf2 target gene products are known regulators of NFkappaB nuclear activity, our results suggest that Ni(II) may affect cytokine secretion indirectly via modulation of the Nrf2 pathway.

Cell Line↗
PubMed2005

Extracellular environment as one mediator of blue light-induced mitochondrial suppression.

OBJECTIVES: The current study tested the hypothesis that the extracellular environment mediates mitochondrial suppression of oral epithelial cells and fibroblasts by blue light. METHODS: We exposed Balb fibroblasts (Balb), normal human epidermal keratinocytes (NHEK), and oral squamous carcinoma cells (OSC2) to blue light (30-120J/cm2) in different cell-culture media and in phosphate buffered saline (PBS). Mitochondrial activity (MTT method) was used to assess cellular response 72 h post-light exposure. Cell-culture media were replaced or supplemented before or after light exposure to assess the variables of exposure time and medium degradation as mediators of blue light-induced effects. RESULTS: Mitochondrial activity of NHEK was not suppressed by exposure to blue light regardless of extracellular conditions. The mitochondrial activity of OSC2 and Balb cells was suppressed most when cells were exposed to light in cell-culture medium (versus PBS). Blue light suppressed mitochondrial activity more when irradiated medium remained in contact with the cells at least 1h, indicating a time-dependence of the medium effects. Neither a replacement nor a supplementation of medium components reduced blue light-induced mitochondrial suppression. SIGNIFICANCE: Our results suggest that tissue environments influence cellular responses to blue light and that these environments should be considered when assessing any biological effects of blue light during the photopolymerization of restorative resins.

Animals↗
PubMed2005

Blue light differentially alters cellular redox properties.

Blue light (lambda = 380-500 nm) historically has been used to initiate polymerization of biomaterials and recently has been proposed as a therapeutic agent. New evidence suggests that cell-type-specific responses result from redox changes induced by exposure to blue light. Cultured cells were exposed to defined doses of blue light, equivalent to exposure times of 10 s and 2 min, to achieve energies of 5 J/cm2 and 60 J/cm2, respectively, after which (a) viable cell number, (b) cellular protein profiles, (c) mitochondrial succinate dehydrogenase (SDH) activity, (d) total reactive oxygen species (ROS), and (e) induction of apoptosis were compared to that of nonexposed control cultures. Results showed that blue-light exposure arrested monocyte cell growth and increased levels of peroxiredoxins. SDH activity of normal epidermal keratinocytes (NHEK) was slightly enhanced by blue light, whereas identical treatment of OSC2 oral tumor cells resulted in significant suppression of SDH activity. Blue-light exposure generally induced higher levels of total ROS in OSC2 cells than in NHEK. Finally, only OSC2 cells exhibited signs of apoptosis via Annexin V staining following exposure to blue light. These data support the central hypothesis that blue light induces an oxidative stress response in cultured cells resulting in cell-type-specific survival outcomes. The identification of oxidative stress as a mediator of the effects of blue light is a critical first step in defining its biological risks and therapeutic opportunities.

Apoptosis↗
PubMed2005

Blue light generates reactive oxygen species (ROS) differentially in tumor vs. normal epithelial cells.

OBJECTIVES: Blue light of high intensity is commonly used in dentistry to activate polymerization of resin restorative materials. Other than its effects on the retina, the biological effects of blue light (380-500nm wavelengths) are poorly studied. Limited evidence suggests that blue light acts by forming intracellular reactive oxygen species (ROS) that then affect critical cell functions. If the biological effects of blue light are redox-mediated, antioxidants might be used to mitigate unwanted side effects of blue light during clinical use, or blue light might be used therapeutically to modulate redox-sensitive cell signaling responses. METHODS: Intracellular ROS were estimated using HFLUOR-DA (dihydrofluorescein diacetate), a vital fluorescein-based, redox-sensitive dye. ROS were measured in normal (NHEK) and oral squamous carcinoma (OSC2) epithelial cells, shown previously to respond differentially to blue light irradiation. Two-hour cumulative levels of ROS and approximate ROS lifetimes were measured after irradiation doses of 5-30 J/cm(2). The blue light-induced generation of ROS was further tested by the ability of the antioxidants N-acetylcysteine (NAC) and vitamin E to mitigate intracellular ROS levels. RESULTS: Dose-dependent ROS levels were generated in both NHEK and OSC2 cells, but cumulative levels were higher and persisted longer in the OSC2 cells. Both vitamin E and NAC significantly reduced blue-light-induced levels of ROS, but were more effective in the OSC2 cells. SIGNIFICANCE: The induction of intracellular ROS by blue light implies that redox effects may mediate cellular responses to blue light. This result suggests the opportunity to mitigate any effects of direct or coincident exposure during dental treatment via antioxidants, and the opportunity to exploit differences in redox processing among cells for possible treatment of epithelial cancer or wound healing.

Antioxidants↗
PubMedDate not supplied

Chemoprevention of oral cancer by green tea.

Green tea has been a popular beverage for many centuries. Only recently, however, has the anti-cancer power of green tea constituents been unveiled. Green tea polyphenols are found to induce apoptosis (programmed cell death) in many types of tumor cells, including oral cancer cells. However, mechanisms that enable normal cells to evade the apoptotic effect still are not understood. In this study, cell growth and invasion assays combined with apoptosis assays were used to examine the effects of green tea extracts, green tea polyphenols, and the most potent green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on normal human keratinocytes and oral carcinoma cells. The results showed that green tea and its constituents selectively induce apoptosis only in oral carcinoma cells, while EGCG was able to inhibit the growth and invasion of oral carcinoma cells. These differential responses to green tea and its constituents between normal and malignant cells were correlated with the induction of p57, a cell cycle regulator. These data suggest that the chemopreventive effects of green tea polyphenols may involve a p57 mediated survival pathway in normal epithelial cells, while oral carcinoma cells undergo an apoptotic pathway. Therefore, regular consumption of green tea could be beneficial in the prevention of oral cancer.

Antineoplastic Agents, Phytogenic↗