Z-VAD-FMK

Z-VAD-FMK (10 μM) inhibits apoptosis in THP.1 cells. This compound (10 μM) inhibits activation of PARP protease activity in control THP.1 cell lysates. It (10 μM) inhibits the processing of CPP32 in intact THP.1 and Jurkat cells. ^[1] This chemical (50 μM) cotreatment abolishes the apoptotic morphology of camptothecin-treated HL60 cells. It (50 μM) blocks camptothecin-induced DNA fragmentation in HL60 cells. ^[2] The compound (50 μM) inhibits cell death following dSMN dsRNA-induced apoptosis in S2 cells. It (50 μM) increases the percentage of transfected cells surviving from 26% to 63% in S2 cells. ^[3] This inhibitor (> 100 μM) enhances TNFα-induced neutrophil apoptosis, lower concentrations (1-30 μM) completely blocks TNFα-stimulated apoptosis in human neutrophils. ^[4] It (10 mM) inhibits apoptosis in anterior stromal keratocytes. The chemical (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 this compound delays preterm delivery in mice. In OVA-sensitized mice,treatment of this chemical inhibits allergen-induced leukocyte infiltration. Systemic injection of this compound immediately before OVA challenge reduced inflammatory cell accumulation, mucus hypersecretion, and Th2 cytokine release in OVA-sensitized/challenged mice. Treatment with this compound blocked terminal differentiation of lens epithelial cells and keratinocytes, the differentiation of monocytes into macrophages, and the differentiation of erythroid progenitors. This chemical attenuated allergen-induced airway inflammation and hyperreactivity. Treatment with this compound 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 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 this compound. 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.