Faculty Bibliography

Disruption of endoplasmic reticulum (ER) homeostasis causes accumulation of unfolded and misfolded proteins in the ER, triggering the ER stress response, which can eventually lead to apoptosis when ER dysfunction is severe or prolonged. Here we demonstrate that human MCF-7 breast cancer cells, as well as murine NIH/3T3 fibroblasts, are rescued from ER stress-initiated apoptosis by insulin-like growth factor-I (IGF-I). IGF-I significantly augments the adaptive capacity of the ER by enhancing compensatory mechanisms such as the IRE1 alpha-, PERK- and ATF6-mediated arms of ER stress signalling. During ER stress, IGF-I stimulates translational recovery and induces expression of the key molecular chaperone protein Grp78/BiP, thereby enhancing the folding capacity of the ER and promoting recovery from ER stress. We also demonstrate that the antiapoptotic activity of IGF-I during ER stress may be mediated by a novel, as yet unidentified, signalling pathway(s). Application of signal transduction inhibitors of MEK (U1026), PI3K (LY294002 and wortmannin), JNK (SP600125), p38 (SB203580), protein kinases A and C (H-89 and staurosporine) and STAT3 (Stattic) does not prevent IGF-I-mediated protection from ER stress-induced apoptosis. Taken together, these data demonstrate that IGF-I protects against ER stress-induced apoptosis by increasing adaptive mechanisms through enhancement of ER stress-signalling pathways, thereby restoring ER homeostasis and preventing apoptosis.

The study set out to examine the predictive effects of patients' emotional distress and their relationships with their health care providers on satisfaction with obstetric services in high-risk pregnancies. Participants were 104 pregnant women with a history of recurrent losses, fetal demise, previous or current fetal genetic abnormality, advanced maternal age, or obstetric or medical complications of the present pregnancy. Self-report measures of emotional distress and the quality of their relationships with their medical provider were administered. Hierarchical multiple regression analyses were conducted to assess the predictive effect of these variables on satisfaction with services. Provision of information, constructive communication, and good relationships predicted elevated satisfaction with health services. Provision of information also buffered against the adverse effect of emotional distress on satisfaction with health services. These findings elucidate the central role of provider patient interaction, particularly as it is related to provision of information, in high-risk pregnancy.