Z-VAD-FMK

Z-VAD-FMK (10 μM) inhibits apoptosis in THP.1 cells. Z-VAD-FMK (10 μM) inhibits activation of PARP protease activity in control THP.1 cell lysates. Z-VAD-FMK (10 μM) inhibits the processing of CPP32 in intact THP.1 and Jurkat cells. ^[1] Z-VAD-FMK (50 μM) cotreatment abolishes the apoptotic morphology of camptothecin-treated HL60 cells. Z-VAD-FMK (50 μM) blocks camptothecin-induced DNA fragmentation in HL60 cells. ^[2] Z-VAD-FMK (50 μM) inhibits cell death following dSMN dsRNA-induced apoptosis in S2 cells. Z-VAD-FMK (50 μM) increases the percentage of transfected cells surviving from 26% to 63% in S2 cells. ^[3] Z-VAD-FMK (> 100 μM) enhances TNFα-induced neutrophil apoptosis, lower concentrations (1-30 μM) completely blocks TNFα-stimulated apoptosis in human neutrophils. ^[4] Z-VAD-FMK (10 mM) inhibits apoptosis in anterior stromal keratocytes. Z-VAD-FMK (10 mM) inhibits apoptosis in anterior stromal keratocytes detected with the TUNEL assay. ^[5]

In vivo Z-VAD-FMK administration has been shown previously to be nontoxic and to prevent apoptosis in animal models. Intraperitoneal HK-GBS injection leads to preterm delivery, and pretreatment with Z-VAD-FMK delays preterm delivery in mice. In OVA-sensitized mice,treatment of z-VAD-fmk inhibits allergen-induced leukocyte infiltration. Systemic injection of the pan-caspase inhibitor z-VAD-fmk immediately before OVA challenge reduced inflammatory cell accumulation, mucus hypersecretion, and Th2 cytokine release in OVA-sensitized/challenged mice. Treatment with z-VAD-fmk blocked terminal differentiation of lens epithelial cells and keratinocytes, the differentiation of monocytes into macrophages, and the differentiation of erythroid progenitors. z-VAD-fmk attenuated allergen-induced airway inflammation and hyperreactivity. Treatment with z-VAD-fmk in vivo also prevented subsequent T cell activation ex vivo^[7].

• Cell lines

  human granulosa cell lines (GC1a, HGL5, COV434)

• Concentrations

  50 μM

• Incubation Time

  48 h

• Method

  To validate the efficacy of Z-VAD-FMK, three human granulosa cell lines (GC1a, HGL5, COV434) were treated for 48 h with etoposide (50 μg/ml) and/or Z-VAD-FMK (50 μM) under normoxic conditions. To mimic the ischemic phase that occurs after ovarian fragment transplantation, cells were cultured without serum under hypoxia (1 % O2) and treated with Z-VAD-FMK. The metabolic activity of the cells was evaluated by WST-1 assay. Cell viability was determined by FACS analyses. The expression of apoptosis-related molecules was assessed by RT-qPCR and Western blot analyses.

• Animal Models

  CD1 mice

• Dosages

  10 mg/kg

• Administration

  i.p.