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S D Shaw

Publications and source records attributed to S D Shaw.

5 recordsLinked to original sources
PubMed2000

Glutathione oxidation and mitochondrial depolarization as mechanisms of nordihydroguaiaretic acid-induced apoptosis in lipoxygenase-deficient FL5.12 cells.

Nordihydroguaiaretic acid (NDGA) induces apoptosis in a variety of cell lines. The mechanism(s) of this effect is not known, although the focus has been on the ability of NDGA to inhibit lipoxygenase (LOX) activities. In the present study, NDGA-induced apoptosis was studied in a murine hematopoietic cell line, FL5.12. Although this cell line lacks detectable LOX protein or activities, NDGA (10 microM) was able to induce apoptosis. There was a massive loss of mitochondrial membrane potential by 4 h after the addition of NDGA, suggesting that this organelle might be targeted by NDGA. A pro-oxidant NDGA effect has been suggested as playing a role in apoptosis. This was supported by the findings that glutathione disulfide levels were increased by 4 h following treatment with 10 microM NDGA, that pretreatment with N-acetylcysteine completely blocked the NDGA-induced loss of membrane potential and apoptosis, and that lipid peroxidation was enhanced in cells treated with NDGA. However, no evidence of increased levels of reactive oxygen could be seen in NDGA-treated cells loaded with dichlorofluorescin diacetate or dihydrorhodamine and analyzed by flow cytometry. Bcl-X(L) protein levels were unaffected by NDGA treatment. Caspase-3 was rapidly activated with a peak at 8 h after FL5.12 cells were treated with NDGA. Ac-DEVD-CHO (25 microM) and boc-asp-FMK (20 microM) both inhibited caspase-3 enzyme activity by 97% 8 h after NDGA treatment. Boc-asp-FMK, a more general caspase inhibitor, delayed NDGA-induced apoptosis while Ac-DEVD-CHO, a more specific inhibitor of caspase-3, had no effect. These results suggest that NDGA-induced apoptosis happens through reactions that depolarize mitochondria, oxidize glutathione and lipids, but do not generate significant amounts of free reactive oxygen species.

Acetylcysteine↗
PubMed1998

Environmental occurrence and potential toxicity of planar, mono-, and di-ortho polychlorinated biphenyls in the biota.

Four non-ortho-, eight mono-ortho-, and two di-ortho-chlorinated congeners have been determined in fresh water and salt water mussels, fish, snapping turtles, mallard, seals, and in human milk and adipose tissue. The planar PCB congeners are separated from the remainder of PCBs by activated carbon chromatography or HPLC on porous graphitic carbon followed by gas chromatography with electron capture detection. PCB toxic equivalency factors (TEFs) recommended by WHO [1] for 3 non-ortho, 8 mono-ortho, and 2 di-ortho PCBs and a TEF for congener 81 suggested by Harris et al. [2] were used for calculation of the contribution to dioxin-like toxicity to each life form. In all the biota examined, PCB congener IUPAC number 126 was the major contributor to PCB toxic equivalents. Congeners IUPAC number 118, 114, 105, 156, 157, 77, 81, and 170 also contributed significantly to PCB toxic equivalents. The ability to separate out planar PCBs from the majority of PCBs has allowed the use of TCDD toxicity equivalence to compare the relative dioxin-like potency of PCB residues in various species from different locations.

Adipose Tissue↗