Bcl-xL functions downstream of caspase-8 to inhibit Fas- and tumor necrosis factor receptor 1-induced apoptosis of MCF7 breast carcinoma cells.

Stimulation of the Fas or tumor necrosis factor receptor 1 (TNFR1) cell surface receptors leads to the activation of the death effector protease, caspase-8, and subsequent apoptosis. In some cells, Bcl-xL overexpression can inhibit anti-Fas- and tumor necrosis factor (TNF)-alpha-induced apoptosis. To address the effect of Bcl-xL on caspase-8 processing, Fas- and TNFR1-mediated apoptosis were studied in the MCF7 breast carcinoma cell line stably transfected with human Fas cDNA (MCF7/F) or double transfected with Fas and human Bcl-xL cDNAs (MCF7/FB). Bcl-xL strongly inhibited apoptosis induced by either anti-Fas or TNF-alpha. In addition, Bcl-xL prevented the change in cytochrome c immunolocalization induced by anti-Fas or TNF-alpha treatment. Using antibodies that recognize the p20 and p10 subunits of active caspase-8, proteolytic processing of caspase-8 was detected in MCF7/F cells following anti-Fas or TNF-alpha, but not during UV-induced apoptosis. In MCF7/FB cells, caspase-8 was processed normally while processing of the downstream caspase-7 was markedly attenuated. Moreover, apoptosis induced by direct microinjection of recombinant, active caspase-8 was completely inhibited by Bcl-xL. These data demonstrate that Bcl-xL can exert an anti-apoptotic function in cells in which caspase-8 is activated. Thus, at least in some cells, caspase-8 signaling in response to Fas or TNFR1 stimulation is regulated by a Bcl-xL-inhibitable step.

Sex differences in attitudes towards newborn infants among women of Mexican origin.

PIP: This paper analyzes a data set on women of Mexican origin delivering in Los Angeles hospitals, in order to examine whether Mexican women's attitudes toward their 1st-born infants are influenced by the sex of the child, either alone or in combination with other factors, such as the difficulty of labor and delivery or the woman's social support system. The authors' hypothesize that the mother's attitude toward the 1st child will be determined primarily by factors other than the child's sex, since there is evidence to suggest equal sex preference among women in Latin culture. They predict that the most negative attitudes would be expressed in the case of an unplanned pregnancy, of a child being born into an unstable family or with physical abnormalities. The women described in this paper are all from the Mestizo, or Hispanicized peoples from Mexico. The analyses are based on interviews with a sample of 518 low risk women. Data on the medical course of their labor and delivery was also collected from their medical charts. The operationalization and measurement of each predictive variable are explained. Sex differences in women's evaluations of their children were examined with Chi-Square analyses. As expected, almost no differences on any attitude measure were found. In general the mothers were very pleased with their infants, whether male or female, although there is a suggestion that if they were disappointed, they were more likely to be displeased with a female infant than with a male. Regression analyses, more sensitive for picking up sex differences than the simple Chi-Square, were performed to determine which of the predictive variables were most related to the mother's attitude. Results show that sex was not a predictive variable. Contrary to what was predicted, whether or not the baby was planned, appeared to be relatively unimportant in the mother's attitude toward her child. A 2nd surprising finding was that the woman's experience of birth was unrelated to her evaluation of her child. The social support system had a significant impact on the mother's evaluation of her child. For both boys and girls, social support from the baby's father was associated with a positive attitude toward infants. Women were significantly more negative toward their infants if they had a poor relationship with the baby's father. Finally, the more acculturated women expressed less positive attitudes toward their newborns; this relationship was slightly stronger for girls than boys.^ieng