Article

Calcium and reactive oxygen species mediated Zn2+ -induced apoptosis in PC12 cells.

Department of Clinical Pharmacy, Tokushima University Hospital, Japan.
Journal of Pharmacological Sciences (impact factor: 2.08). 10/2006; 102(1):103-11. pp.103-11
Source: PubMed

ABSTRACT The release of excessive Zn(2+) from presynaptic boutons into extracellular regions contributes to neuronal apoptotic events, which result in neuronal cell death. However, the mechanisms of Zn(2+)-induced neuronal cell death are still unclear. Therefore, we investigated the dynamics of intracellular Zn(2+), calcium, and reactive oxygen species in PC12 cells. The addition of Zn(2+) produced cell death in a concentration- and time-dependent manner. (45)Ca(2+) influx occurred just after the treatment with Zn(2+), although subsequent hydroxyl radical ((*)OH) production did not begin until 3 h after Zn(2+) exposure. (*)OH production was significantly attenuated in Ca(2+)-free medium or by L-type Ca(2+) channel antagonist treatment, but it was independent of the intracellular Zn(2+) content. Dantrolene treatment had no protective effects against Zn(2+)-induced cell death. Treatment with N-acetyl-L-cysteine blocked (*)OH generation and subsequent cell death. These data indicate that Ca(2+) influx and subsequent (*)OH production are critical events in Zn(2+)-induced toxicity in PC12 cells.

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    Article: Antioxidant combinations protect oral fibroblasts against metal-induced toxicity.
    Symone M San Miguel, Lynne A Opperman, Edward P Allen, Jan E Zielinski, Kathy K H Svoboda
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    ABSTRACT: OBJECTIVE: In dentistry, the use of metals in fillings, braces, implants, bridges and other prosthodontic restorations is a common practice. Previous studies revealed that zinc (Zn) and copper (Cu) released from gold alloys, and nickel (Ni) released from nickel-chromium alloys, have a highly cytotoxic effect on fibroblast cell cultures. Our working hypothesis is that oral fibroblasts are susceptible to damage from metals because they elevate reaction oxygen species (ROS). In this study, we investigated specific antioxidant (AO) combinations to determine if they counteract the effects of Cu, Ni and Zn on cultured oral fibroblast proliferation and oxidative damage. METHODS: Oral fibroblasts were pretreated with Cu, Ni and Zn for 60min. Thereafter, cells were treated with 10(-5)M combinations of bioactive AO resveratrol (R), ferulic acid (F), phloretin (P) and tetrahydrocurcuminoids (T) (RFT, PFR, PFT) for 24h. Cell viability and DNA synthesis were monitored by 3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium (MTS) and 5-bromo-2-deoxyuridine (BrDU) assays. ROS was measured using the fluorescence response of dichlorodihydrofluorescein diacetate (DCF). RESULTS: AO compounds increased recovery of cells exposed to Cu and Zn. Moreover, AO treatment induced DNA synthesis in the presence of the metal stressors. Cu and Ni stimulated production of ROS. PFR treatment decreased ROS in the presence of Cu, Ni and Zn. SIGNIFICANCE: These data indicate that pure AOs counteracted the detrimental effects of Cu, Ni, Zn on oral fibroblasts in vitro by increasing cell viability, and DNA synthesis and decreasing ROS activity.
    Archives of oral biology 07/2012; · 1.65 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Keywords

cell death
 
concentration-
 
Dantrolene treatment
 
extracellular regions contributes
 
intracellular Zn(2+)
 
N-acetyl-L-cysteine
 
neuronal apoptotic events
 
neuronal cell death
 
presynaptic boutons
 
protective effects
 
reactive oxygen species
 
subsequent
 
subsequent cell death
 
subsequent hydroxyl radical
 
Zn(2+)-induced cell death
 
Zn(2+)-induced neuronal cell death
 
Zn(2+)-induced toxicity