The possible apoptosis pathways of Bombyx mori The apoptosis related factors identified in silkworms cover almost all the critical DZNeP chemical structure junctions in the apoptosis pathways of other model organisms. Although Fas and its receptor were not found, we found some proteins predicted containing cysteine regions, Ca2 binding sites, or the typical receptor ligand interaction sites of TNFRSF members, downstream genes such as BmTraf family members and BmFadd, which contain DDs, and BmDredd. All these results suggest that the death receptor pathway may be present in Bom byx mori. We hypothesize that the epidermal growth factor pathway also exists in Bombyx mori, because homologs of the mammalian members of this pathway were cloned and identified in Bombyx mori, including BmRaf, BmRas, BmPka, BmPkc, BmErk, BmPi3k, BmStat, BmAkt, BmGsk3, and BmFkhr.

The Bombyx mori homologs of Cyt C, Apaf 1, Caspase 9, Aif, Endo G, and Htra2 were identified and characterized in Bom byx mori, and Kumarswamy and colleagues and the Pan group have demonstrated cytochrome C release into the cytoplasm in stress induced apoptotic Sf 9 and BmE cells. Therefore, the mitochondrial apoptotic path way may be functional Inhibitors,Modulators,Libraries in Bombyx mori. Furthermore, the DmReaper orthologs found in Bombyx mori indicate that this apoptotic gene is conserved between species. In addition, key genes in the DNA damage response path way, like BmP53 and BmSir2, are also identified, so we hypothesize that the DNA damage pathway is also func tional in Bombyx mori. In conclusion, the intrinsic and extrinsic pathways described in other models may potentially exist in Bombyx mori.

In 1965 silkworm hemolymph was used Inhibitors,Modulators,Libraries as an addi tional agent in cell culture in vitro. Rhee and col leagues confirmed that silkworm hemolymph inhibited cell apoptosis not only in a baculovirus induced insect cell system but also in a human cell system. In 2002, this group reported that they isolated and charac terized an apoptosis Entinostat inhibiting hemolymph component. Later they constructed a recombinant vector to express the protein and purify it in vitro, and confirmed this protein is one of the 30K proteins isolated from silkworm hemolymph used to minimize cell death. They speculated that the 30Kc6 protein inhibits the apoptosis by involvement upstream of caspase3 activation. Therefore, there might be differences between Bombyx mori and other models in the regulation of apoptosis.

Questions remain as to the precise regulation of apopto sis in Bombyx mori, for example, the central Inhibitors,Modulators,Libraries role of BmReaper, as well its homolog in Drosophila, Inhibitors,Modulators,Libraries and whether BmCytC is released from the mitochondria as in mammals. Also, the BH3 only Bcl 2 family members that link the two primary apoptotic SKI-606 pathways are not found in Bombyx mori and have not been reported in insects.