Tert-Butyl Hydroperoxide Stimulated Apoptosis Independent of Prostaglandin E2 and IL-6 in the HTR-8/SVneo Human Placental Cell Line.
Reprod Sci
; 27(11): 2104-2114, 2020 11.
Article
en En
| MEDLINE
| ID: mdl-32542535
ABSTRACT
Significant gaps exist in our knowledge of how cellular redox status, sometimes referred to as oxidative stress, impacts placental trophoblasts. The present study used tert-butyl hydroperoxide (TBHP) as a known generator of reactive oxygen species (ROS) in the extravillous trophoblast cell line HTR-8/SVneo to examine the role of cellular redox disruption of prostaglandin E2 (PGE2) and the cytokine IL-6 in cell death. Cells were exposed to 0, 12.5, 25, or 50 µM TBHP for 4, 8, and 24 h to ascertain effects on cell viability, caspase 3/7 activity, PGE2 release, PTGS2 mRNA expression, and IL-6 release. Experiments with inhibitors included the cyclooxygenase inhibitor indomethacin, mitogen-activated protein kinase inhibitors (PD169316, U0126, or SP600125), or treatments to counter expected consequences of TBHP-stimulated generation of ROS (deferoxamine [DFO], butylated hydroxyanisole [BHA], and N,N'-diphenyl-1,4-phenylenediamine [DPPD]) using 24-h exposure to 50 µM TBHP. Cell viability, measured by ATP content, decreased 24% relative to controls with a 24-h exposure to 50 µM TBHP, but not at lower TBHP concentrations nor at earlier time points. Exposure to 50 µM TBHP increased caspase 3/7 activity, an indicator of apoptosis, after 8 and 24 h. Antioxidant treatment markedly reduced TBHP-stimulated caspase 3/7 activity, PGE2 release, and IL-6 release. TBHP-stimulated IL-6 release was blocked by PD169316 but unaltered by indomethacin. These data suggest that TBHP-stimulated IL-6 release and caspase 3/7 activation were independent of PGE2 yet were interrupted by treatments with known antioxidant properties, providing new insight into relationships between PGE2, IL-6, and apoptosis under conditions of chemically induced cellular oxidation.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Placenta
/
Trofoblastos
/
Dinoprostona
/
Interleucina-6
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Especies Reactivas de Oxígeno
/
Apoptosis
/
Terc-Butilhidroperóxido
Límite:
Female
/
Humans
/
Pregnancy
Idioma:
En
Revista:
Reprod Sci
Asunto de la revista:
MEDICINA REPRODUTIVA
Año:
2020
Tipo del documento:
Article
País de afiliación:
Estados Unidos