Modulation of gap junction transcript and protein expression during pregnancy in the rat

Abstract. The expression of three different gap junction transcripts, or, (Cx43), B ~ (Cx39, and B2 (Cx26) was examined in several organs during pregnancy in the rat. In all of the organs that were examined-uterus, ovary, heart, and liver-there was a strong correlation between levels of gap junction mRNA and gap junction antigens that were detected at different stages of pregnancy. A striking change in o ~ transcript levels (a 5.5-fold increase) was detected in the uterine myometrium on the day before parturition. This elevation of the c~, transcript is thought to be associated with the formation of gap junctions that are required for synchronizing the contractility of the myometrial cells during parturition. 2 d before parturition, there was a detectable elevation of/32 transcripts and protein in th

Androgen Receptor-Mediated Apoptosis Is Regulated by Photoactivatable Androgen Receptor Ligands

We have studied nonsteroidal ligands of the human androgen receptor (hAR) and have shown elsewhere that when photoactivated by visible light they collide with O2 to yield singlet oxygens (1O2) in vitro. Here we report cell killing after brief light activation (405 nm) of 1,2,3,4-tetrahydro-2,2-dimethyl-6-(trifluoromethyl)-8-pyridono[5,6-g]quinoline (TDPQ) in human prostate tumor cells. TDPQ/AR complexes were required for the death response because AR-positive LNCaP cells were killed, whereas AR-negative PC-3 cells were resistant. Excess dihydrotestosterone (DHT) blocked the TDPQ effect when the two were added together; irradiation of cells containing DHT alone had no effect. When LNCaP AR expression was suppressed using small interfering oligonucleotides targeting AR, photocytotoxicity was diminished. Conversely, stable transfection of hAR into PC-3 cells made the cells photosensitive to TDPQ. Similar results were obtained using a structural isomer of TDPQ, and also the synthetic steroidal AR ligand R1881. Cell death occurred via apoptosis as demonstrated by annexin V immunostaining, nuclear condensation, and caspase inhibition. Death involved oxidative stress, because it was prevented by addition of the antioxidant ascorbic acid during photoactivation. Detection of elevated levels of 8-hydroxy-2′-deoxyguanosine in nuclei of irradiated cells indicated oxidative DNA damage. Apoptosis spread into adjacent nonirradiated cells by direct cell-cell contacts, indicative of a bystander effect. Other photoactivatable ligands are described, implying a general method for ablation of cells bearing specific nuclear hormone receptors

Gap junction formation in human myometrium: a key to preterm labor?

OBJECTIVE: The purpose of this study was to determine if gap junctions are a necessary component of the human laboring uterus and if their presence in myometrium is a prerequisite for both term and preterm labor. STUDY DESIGN: We obtained 27 human myometrial samples at cesarean section or nongravid hysterectomy. Gap junction formation was analyzed in a blind fashion by freeze fracture and indirect immunofluorescence. Six samples were obtained from term patients with no labor, six from term patients in labor, six from preterm patients with no labor, six from patients in preterm labor, and three from nongravid hysterectomy specimens. RESULTS: Gap junction structures were identified in the human myometrium of patients in term and in preterm labor but not in the other patient samples. In addition, evidence was obtained for the expression of (alpha 1) gap junction ribonucleic acid and (alpha 1) gap junction protein in term samples of human myometrium. CONCLUSION: Gap junctions are a necessary component of the human myometrium during term and preterm labor. The formation of gap junctions may be a final common event for the development of labor, and inhibition of gap junction activity could be a novel approach for the treatment of preterm labor