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Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model.

Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E - Infect Dis Obstet Gynecol (2009)

Bottom Line: Objective.The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org

ABSTRACT
Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

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Apoptosis in the ovarian follicle. Mouse atretic follicles are known to undergo caspase mediated apoptosis. As anticipated, caspase 3 was cleaved and activated in the atretic follicle, which were used as positive control for the caspase 3 antibody specificity. Representative data from three separate experiments are shown.
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fig4: Apoptosis in the ovarian follicle. Mouse atretic follicles are known to undergo caspase mediated apoptosis. As anticipated, caspase 3 was cleaved and activated in the atretic follicle, which were used as positive control for the caspase 3 antibody specificity. Representative data from three separate experiments are shown.

Mentions: Caspase 3 is the common executioner caspase activated by both the extrinsic (Fas) and intrinsic (mitochondrial) caspase machinery. Intrauterine HK-GBS exposure induced caspase 3 activation in a time-dependent manner (i.e., at 14 hours but not 5 hours) in the fetal membranes (Figures 3; 3(a)–3(c)) and in the placenta (Figures 3; 3(d)–3(f)) as assessed by immunohistochemistry using an antibody specific for activated cleaved caspase 3. In order to confirm the specificity of the caspase 3 staining, we used nonpregnant mouse ovaries as positive control tissue. As anticipated, caspase 3 was activated in the atretic ovarian follicles (Figure 4).


Pretreatment with pancaspase inhibitor (Z-VAD-FMK) delays but does not prevent intraperitoneal heat-killed group B Streptococcus-induced preterm delivery in a pregnant mouse model.

Equils O, Moffatt-Blue C, Ishikawa TO, Simmons CF, Ilievski V, Hirsch E - Infect Dis Obstet Gynecol (2009)

Apoptosis in the ovarian follicle. Mouse atretic follicles are known to undergo caspase mediated apoptosis. As anticipated, caspase 3 was cleaved and activated in the atretic follicle, which were used as positive control for the caspase 3 antibody specificity. Representative data from three separate experiments are shown.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2801448&req=5

fig4: Apoptosis in the ovarian follicle. Mouse atretic follicles are known to undergo caspase mediated apoptosis. As anticipated, caspase 3 was cleaved and activated in the atretic follicle, which were used as positive control for the caspase 3 antibody specificity. Representative data from three separate experiments are shown.
Mentions: Caspase 3 is the common executioner caspase activated by both the extrinsic (Fas) and intrinsic (mitochondrial) caspase machinery. Intrauterine HK-GBS exposure induced caspase 3 activation in a time-dependent manner (i.e., at 14 hours but not 5 hours) in the fetal membranes (Figures 3; 3(a)–3(c)) and in the placenta (Figures 3; 3(d)–3(f)) as assessed by immunohistochemistry using an antibody specific for activated cleaved caspase 3. In order to confirm the specificity of the caspase 3 staining, we used nonpregnant mouse ovaries as positive control tissue. As anticipated, caspase 3 was activated in the atretic ovarian follicles (Figure 4).

Bottom Line: Objective.The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta.Conclusion.

View Article: PubMed Central - PubMed

Affiliation: Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. ozlem.equils@cshs.org

ABSTRACT
Caspases and apoptosis are thought to play a role in infection-associated preterm-delivery. We have shown that in vitro treatment with pancaspase inhibitor Z-VAD-FMK protects trophoblasts from microbial antigen-induced apoptosis. Objective. To examine whether in vivo administration of Z-VAD-FMK would prevent infection-induced preterm-delivery. Methods. We injected 14.5 day-pregnant-mice with heat-killed group B streptococcus (HK-GBS). Apoptosis within placentas and membranes was assessed by TUNEL staining. Calpain expression and caspase-3 activation were assessed by immunohistochemistry. Preterm-delivery was defined as expulsion of a fetus within 48 hours after injection. Results. Intrauterine (i.u.) or intraperitoneal (i.p.) HK-GBS injection led to preterm-delivery and induced apoptosis in placentas and membranes at 14 hours. The expression of calpain, a caspase-independent inducer of apoptosis, was increased in placenta. Treatment with the specific caspase inhibitor Z-VAD-FMK (i.p.) prior to HK-GBS (i.p.) delayed but did not prevent preterm-delivery. Conclusion. Caspase-dependent apoptosis appears to play a role in the timing but not the occurrence of GBS-induced preterm delivery in the mouse.

Show MeSH
Related in: MedlinePlus