The mix of tropisetron and 9 THC didn’t supply a higher antiemetic effect than that obtained using the drugs given individually. This is consistent with the view the antiemesis mediated by cannabinoids reaches least partly because of blockade of 5 HT3 receptors. Some steroidsmay modify neuronal excitability via interaction with neurotransmitter receptors, i. e., and others members of the ligand gated ion channel family. It’s well established that particular steroids are positive or negative allosteric modulators of GABAA receptors and of nACh receptors. In example, it’s been proven a number of compounds have the ability to inhibit agonist induced cation increase Imatinib CGP-57148B through 5 HT3 receptors of varied species in themicromolar concentration range. The identified inhibition constants for the steroid hormones 17B testosterone, progesterone and estradiol as well as for the synthetic glucocorticoid dexamethasone are summarised in Table 3. Steroids have shown to inhibit 5 HT3 receptors in a noncompetitive and voltage independent fashion. An open channel block seems impossible, since inhibition of 5 HT induced currents through 5 HT3A receptors by 17B estradiol only was present after preincubation with the receptor. More over, membranes Metastasis of HEK293 cells expressing murine recombinant 5 HT3A receptors may be branded with steroid?BSA buildings that can’t cross the cell membrane. However, radiolabelled gonadal steroids bound to these 5 HT3A receptors could not measure dependently be displaced by materials. This argues against a saturable steroid binding site in the extra-cellular domain of the receptor. For progesterone it’s been shown that the intracellularly applied drug had no effect on the efficiency of the rat 5 HT3 receptor by extracellularly applied progesterone. Thus, an allosteric interaction of steroids within the receptor? membrane software seems likely. This would be consistent with the highly lipophilic character of these compounds. Lenalidomide clinical trial Barann et al. have examined a series of steroid compounds and reported that the effectiveness on 5 HT3 receptors improves with increasing lipophilicity. Moreover, the steroid strength rate in the 5 HT3A receptor associated with the voltage gated Na channel was less-than 2. 6 for all tested compounds. This supports the hypothesis that steroids connect to membrane lipids within the neighborhood of these ion channels. On the other hand, inhibition of 5 HT3 receptors by steroids can not be attributed simply to their lipophilicity since not all materials have antagonistic properties. Also, 17B estradiol was less potent in the perturbation of membranes when compared to progesterone though it has been proved to be a far more potent inhibitor of the 5 HT3A receptor than progesterone.

The current state of the art shows that different isoforms play unique roles in methods of this process. Efforts of the pharmaceutical industry, as claimed by the growing number of patents in the field, are currently intensifying, the time for the first clinical studies is probable perhaps not too far in the future. 5 Hydroxytryptamine was first called enteramine in the belly. Based on its vasoconstrictive task it was called serotonin. Serotonin exerts Celecoxib clinical trial many different bodily functions not merely in the central and peripheral nervous system but also in the immune system, the aerobic and the gastro-intestinal tract. The serotonergic system is prepared in a highly complex fashion, as 5 HT action is mediated by a multitude of receptor subtypes. These sub-types are split into seven major classes according to their pharmacological, structural and functional characteristics. Except for the 5 HT3 receptor, which really is a ligandgated ion channel, they represent G-protein coupled receptors. More than 50 years ago, the 5 HT3 receptor was described as the so called M receptor in the guinea pig stomach. Since that time our knowledge of 5 HT3 receptor heterogeneity has Metastasis clearly increased. Unravelling the properties of the machine resulting in this difficulty is one of the main objectives of 5 HT research. Particularly targeting receptor sub-types at different internet sites may possibly allow us to target treatments to more specific needs. Recent progress in molecular genetics give a lot more way to private medicine strategies treating complex diseases such as psychological and functional GI disorders together with unravelling individual drug response in pharmacogenetic strategies. In this review we are going to discuss the molecular basis of 5 HT3 receptor diversity at the DNA and protein level, their role in health and illness and describe certain casecontrol studies addressing the contribution of polymorphisms of 5 HT3 subunit genes genes in complex conditions and pharmacogenetic approaches1. Furthermore, the primary focus is the true state of the pharmacological knowledge Chk2 inhibitor concerning not only the traditional 5 HT3 antagonists the setrons but also compounds of various substance courses targeting 5 HT3 receptors such as anaesthetics, opioids, cannabinoids, steroids, antidepressants and anti-psychotics as-well as natural compounds produced fromplantswhich may possibly point out alternative treatments modulating the 5 HT3 receptor process in the future. Due to the proven fact that the 5 HT3 receptor system is equally molecularly and functionally specific between animals and people, we will primarily concentrate on human receptors. Knowledge regarding 5 HT3 receptors of other species have recently been summarised elsewhere. Until 1999, only two individual 5 HT3 subunit genes, and, have been recognized.

The CAChe work process was useful for performing the Extended Huckel molecular orbital calculations. Press was then removed and MTT solution was added followed with a 2 h incubation period. MTT was then removed and 100 ul DMSO added to dissolve the product, followed closely by measuring the absorbance values over a Victor 3 multi label plate reader. The chemical structures were built and compounds were put through geometry optimization. Nucleophilic susceptibility was treated and the electron density surface was colored by nucleophilic susceptibility. The best susceptibility towards nuceophilic assault was signified Imatinib Gleevec by a bulls eye with a white center. Filtered individual 20S proteasome was incubated in 100 ul of assay buffer and 20 uMof chymotrypsin like substrate Suc LLVY AMC, using different levels of Cd1, Cd2 and Cd3 or as a car control DMSO for 2 h at 37 C. Subsequent incubation, proteasome CT like activitywas tested applying theWallac Victor 3 Multi label Counter having an excitation filter of 365 nm and emission filter of 460 nm. MDA and mcf7 MB Plastid 231 cells were treated as indicated, lysed and protein concentrationsmeasured from the Bio Rad Protein Assay. Total cell extracts were incubated for 2 h at 37 C in 100 ul of assay buffer with 20 umol/l fluorogenic peptide substrate Suc LLVY AMC. Proteasomal CT like activity was measured utilizing the Wallac Victor 3 Multi brand Counter with an excitation filter of 365 nm and emission filter of 460 nm. Mobile morphology changes were observed using a Zeiss Axiovert 25 microscope with phase contrast, as previously described. We previously reported the DSF Cd mix could selectively inhibit growth and induce apoptosis in human breast cancer Ibrutinib Src inhibitor cells, but not inside their non tumorigenic counterparts. But, the consequence of artificial Cd complexes on cyst cells has not been studied, and the assessment of Cd to other metals in similar complexes has not been done. We therefore produced three Cd centered compounds: Cd1, Cd2 and Cd3 as well as many related Cu and Zn complexes for an evaluation. The contents of carbon, hydrogen and nitrogen in each complex were measured by an elemental analysis device, which confirmed the structure of these processes. After investigation of the infrared spectra of the synthesized dinuclear material containing buildings, the strong NH assimilation highs did indeed appear in the product range of 3389.91 3408. 16 cm 1 without any apparent shift compared to the ligands. This observation shows that the nitrogen inside the indole ring didn’t form a coordination bond with the metal ions. In comparison, the infrared spectra of the ligands within the metal complexes produced two new peaks at 1539. 23 1591. 13 cm 1 and 1414. 59 1464. 37 cm, 1 which could be caused by as and s, respectively.

Three or four BH domains are possessed by most of the anti apoptotic family members, and most of them also possess a C terminal transmembrane domain that’s accountable for their localization to the cytoplasmic faces of intracellular membranes. The pro apoptotic Bcl 2 members facilitate or immediately induce the permeabilization of the mitochondrial membrane, that leads to the release of caspase activators in the mitochondria thus causing apoptosis. The pro apoptotic Bcl 2 proteins are antagonized by their anti apoptotic competitors which function by binding and sequestering the pro apoptotic Bcl 2 proteins, thus stopping mitochondrial conjugating enzyme membrane permeabilization induced apoptosis. In mouse and human, there are 6 known members of the Bcl2 like anti apoptotic subscription family, which are imperative to the growth and success of lymphoid and myeloid cells. So far, orthologues of Bcl 2, Bcl XL,Mcl 1, and NRH have been determined in fish, and duplications of some members have also occurred possibly as due to teleost specific genome duplication. NR 13 was discovered in quail neuroretina cells as a gene that was induced by Rous sarcoma virus infection. NR 13 gene activation by P60v src or vrel continues to be documented and accounts for the apoptotic inhibition Mitochondrion associated with viral pathogenesis or oncogenesis, respectively. Subsequent reports of NR 13 orthologues in animals proved their jobs as antagonists of apoptosis. Recently, the zebrafish NR 13 orthologue was identified, which was shown to play a key role in development, and antagonize the professional apoptotic Bax. Zebrafish orthologues of Mcl 1 and Bcl XL are also recognized. Along with the anti apoptotic features of Mcl 1 and Bcl XL noticed in zebrafish embryo, over expression of both zebrafish Mcl 1 or Bcl XL secured betanodavirusinfected GL av cells from necrotic cell death. Several pathogen associated molecular patterns, including lipopolysaccharide and double-stranded RNA, are identified inducers of apoptosis using types of fish cells. For instance, in fish lymphocytes, LPS induced apoptosis was found to be connected with down regulation of anti apoptotic Bcl up and 2 expression regulation in proapoptotic Bax expression. The apoptotic effect of polyriboinosinic polyribocytidylic acid has also been demonstrated using rainbow trout macrophage RTS11 cells. In several in vivo studies, similar PAMPs have been used to generate ubiquitin ligase activity immune responses in the host. Our past useful genomic reports involving Atlantic cod stimulated with immunogens led to the identification of numerous expressed sequence tags which can be mixed up in Atlantic cod implicit resistant tissue response. As the analysis of functional annotations associated with major BLAST visits of these previously produced Atlantic cod ESTs suggested the involvement of apoptotic regulation in cod immune reaction to bacterial and viral stimuli, further studies are required to completely understand the part of apoptotic regulation in cod innate immunity.

An initial gate to ensure that only pathogen specific lymphocytes are allowed to proliferate is the requirement of co stimulation. antigen specific lymphocytes multiply broadly, with doubling times as fast as 7 h. It is essential, therefore, that checkpoints are in position to make sure only appropriate lymphocytes are permitted to survive and multiply upon antigen encounter and that expansion of autoreactive natural compound library cells is aborted. Though it is likely to propose that Bcl 2 family members make-up such a checkpoint, the actual involvement of every family member is only now being elucidated. Moreover, there seem to be a lot more checkpoints either ahead or apart of the regulation exerted by Bcl 2 family proteins. Lymphocytes can not absolutely trigger and undergo apoptosis at a higher level, when company arousal fails. While T cells make use of the CD19/C21 complex and CD40, the main co stimulatory molecule for resting T cells is CD28. In line with their role in maintaining cell survival, CD28, CD19 and CD40 derived signals are potent inducers of the Bcl 2 like survival factor Bcl xL. CD40 also induces, possibly via NF W, the expression of Bcl 2 like survival element A1/Bfl Plastid 1 and ergo safeguards B cells from antigen receptor mediated apoptosis. Co pleasure also promotes increased cytokine production, including IL 2 and IL 4, which further increase expression and cell-signaling of survival promoting genes. Most significantly, activation of B and T cells doesn’t only carefully increase the cell numbers but also makes these cells gradually more sensitive for apoptosis. This is because the great majority of the expanded cells are eliminated by apoptosis once they have done their job. Clonal expansion of lymphocytes depends on cytokines including IL 2. Paradoxically, nevertheless, T-cells require IL 2 to the autocrine growth factor to become vulnerable to death in the latter phase of an inflammatory reaction and IL 2 deficiency results in accumulation of activated lymphocytes and autoimmunity. Letrozole structure T cells become increasingly sensitive to Fas induced cell death beginning several days after TCR activation. Furthermore, B cells are sensitized to cell death by activation. It is however controversial whether removal is simply by the death receptor pathway but also by the fall of cytokines. In support of the latter model is the observation that the death of activated growing cells may be eliminated by treatment using a range of cytokines including IL 2, TNF, the sort I interferons and members of the C family. In line with a sensitization to apoptosis following activation, Bcl 2 protein expression is downregulated in primed CD45RO T cells.

As transcription aspect it could stimulate or repress gene products that crucially control apoptosis, and a plethora of such products have been identified. Of the many possible objectives, PUMA and Noxa are certainly the most attractive, but wThe BH3 only death factors are so called since they share with each other and with the other members of the Bcl 2 family of proteins, only the short BH3 domain. In worms, just one person in this subfamily, EGL 1, has thus far been found. This protein plays a dominant and crucial part in the induction of programmed cell death of somatic cells. Biochemical and genetic studies have shown that EGL 1 acts by nestling its BH3 domain into the hydrophobic pocket of CED 9, thus publishing CED 4 for CED 3 caspase activation. Depending on the cell type and the developmental stage, EGL 1 expression ALK inhibitor may be positively or negatively regulated by several transcription factors. Recently, studies on injury induced apoptosis in C. elegans germ cells revealed that although this cell death was dependent on CED 3 and CED 4 and might be restricted by CED 9, it was only partly blocked by EGL 1 lack of function mutations. This means the presence of one or more additional BH3 only proteins in H. As the BH3 area is extremely small and defectively defined elegans, Ribonucleic acid (RNA) however it could be difficult to identify these proteins in searches of sequence databases. The way in which how EGL 1 is controlled and initiates developmental cell death in C. elegans implies that BH3 only proteins act as mediators and devices of apoptotic responses. Indeed, genetic studies have begun to discover that every of the 10 to date discovered BH3 only proteins in mammals might sense another apoptotic government and then relay the sign to multidomain Bcl 2 family members. Just how do they perform this crucial work? It appears that in balanced mammalian cells, BH3 only proteins are kept inert by translational and transcriptional mechanism therefore stopping inappropriate cell deaths. In response to an apoptotic sign, these proteins are activated by one or several of the following mechanisms. One system is by transcriptional induction as known for EGL 1 in D. elegans. Noxa and puma/bbc3 are BH3 only proteins that are activated by p53 and are thus believed to sense a p53 dependent apoptotic signal. contact us p53 is a transcription factor that participates in apoptosis induced by DNA damaging agents including irradiation, UV and chemodrugs. This has been well shown in p53 cells. These cells are generally resistant to DNA damage induced apoptosis, but remain sensitive and painful to apoptosis induced by cytokine starvation or the procedure with TNF/Fas like factors. Furthermore, in Drosophila and C. elegans, p53 homologs mediate a pro apoptotic as opposed to an anti proliferative response. It’s however remained enigmatic how p53 works its professional apoptotic function.

Anxa1 decreases cell proliferation from the instudy showed that the supplementation of GSH to KCL22S cells resulted in an increase from the IC50 worth of imatinib. Anxa1 also belongs to network 1 and was identified by us to get downregulated in KCL22R cells. Annexin A1 is a 37 kDa member of your annexin family members that structurally belongs to a family members of ubiquitous phospholipids and calcium binding proteins.tence of effective cell cycle management machinery. How Plasmodium regulates cell development and di vision pifithrin a remains, nonetheless, largely unknown. The cell cycle of Plasmodium throughout intra erythrocytic proliferation is uncommon in many respects. After the development phase that follows invasion from the erythrocyte by the merozoite, and which brings the parasite through the early ring type on the trophozoite stage the place DNA syn thesis is initiated, successive nuclear divisions arise from the absence of cell division, resulting in a multinucleated schizont. Yet another pecu liarity is the fact that nuclei in a offered schizont divide asynchronously, and nuclei preserve their individuality, because the nuclear envelope is maintained during the nuclear division course of action. Plasmodium has no standard centrioles/centrosomes.

Instead, the mitotic spindles are emitted from spindle pole bodies which can be associated together with the inner side on the nuclear envelope. A clear correspondence between the G1, S, G2 and M phases hasn’t been established, despite the fact that it is actually agreed that rings and early Endosymbiotic theory trophozoites are in G1, and S is initiated in mature trophozoites. The organization of the cell cycle phases in dividing nuclei for the duration of schizontmaturation is as still not understood. Mitosis in eukaryotic cells includes the concerted action of a number of conserved serine/threonine protein kinases regarded as mitotic kinases, which consist of cyclin dependent kinases, Polo like kinases, Nima associated kinases and Aurora kinases. Working with many different bio informatic equipment, 85?99 genes encoding protein kinase connected enzymes while in the P.

falciparum genome were recognized, which unveiled a image of profound divergence concerning Plasmodium and mammalian PKs. On top of that systematic reverse genetics in the total kinome continues to be implemented in both the rodent malaria Q6parasite ATP-competitive ALK inhibitor Plasmodiumberghei and P. falciparum, leading to the establishment of a listing of enzymes critical for asexual proliferation or for particular stages in sexual development. From the current reviewwe focus around the Nima linked and also the Aurora kinase families, each of which are represented with quite a few enzymes in the P. falciparum kinome. The NIMA related protein kinases constitute a family of protein kinases initially recognized as enjoying a range of roles in cell cycle regulation. These proteins are extensively represented in eukaryotes, along with the 1st member of your NIMA family was discovered in the screen for cell cycle mutants from the fungus Aspergillus nidulans.

We directly tested whether Ase1 is necessary for spindle assembly by analyzing SPB separation in deg cin8 ase1D double mutant cells after release into nonpermissive conditions. SPBs did not separate in 90-98 of deg cin8 ase1D cells, while SPB separation was exceedingly temporary in the remaining a large number of cells. Visibly, the phenotype is identical to the degcin8 HDAC2 inhibitor ipl1 315 double mutant phenotype, suggesting that Ipl1 and Ase1 might function together to gather spindles. We also analyzed MT morphology in deg cin8 ase1D stresses and deg cin8 ipl1 315. Just like the previously described phenotype of cin8 kip1 double mutant cells, we found that deg cin8 ipl1 315 and degcin8 ase1D cells demonstrated the long V shaped MTs that are characteristic of monopolar spindles. Ase1 Overexpression Suppresses the deg cin8 ipl1 315 Lethality If Ipl1 and Ase1 act within the same path, we reasoned that Ase1 overexpression may control the deg cin8 ipl1 315 lethality. Certainly, Ase1 overexpression totally suppressed the growth problems of deg cin8 Infectious causes of cancer ipl1315 cells. We reviewed deg cin8 ipl1 315 pGALASE1 cells expressing Spc42 GFP where galactose was added 30 min before release from G1 to concurrently repress deg Cin8 and overexpress Ase1, to confirm that SPB divorce was repaired. Timelapse pictures confirmed the SPBs separated in 80% of the deg cin8 ipl1 315 cells overexpressing Ase1. Moreover, Ase1 overexpression reasonably suppressed the degcin8 kip1D lethality, suggesting that upregulating still another construction path can partly over come the defects related to affected BimC purpose. To find out whether Ase1 might be an Ipl1 goal for spindle assembly, we tested whether Ipl1 directly phosphorylates the protein in vitro. Epitope described Ase1 that Afatinib solubility have been immunoprecipitated was phosphorylated by recombinant Ipl1. We for that reason mutated the five Ipl1 consensus phosphorylation websites in Ase1 to alanine to produce the ase1 5A allele. We reviewed spindle assembly in deg cin8 ase1D cells expressing ase1 5A or ASE1 on centromere based plasmids by time lapse microscopy 60 min after releasing cells from G1 into conditions. A large number of wild type and 90-angle of deg cin8 ase1D cells that have wild type ASE1 maintained divided SPBs throughout the time course, as expected. In contrast, 80-20 of the degcin8 ase1D cells containing ase1 5A never divided their SPBs, much like both cin8 ipl1 315 and cin8 ase1D mutant strains. Immunoblotting confirmed that Ase1 5A was expressed at levels similar to wild type Ase1. For that reason, the Ipl1 consensus websites in Ase1 are very important for spindle assembly. The lack of SPB divorce inside the deg cin8 ase1 5A cells may be described by the possibility that mutating five elements in ASE1 absolutely inactivates its purpose.

information propose that Ipl1 may possibly regulate spindle assembly by the Ase1 protein. Comprehending the precise roles of Aurora B along with the PRC1 isoforms in spindle assembly will consequently be indispensable to both knowing tumorigenesis and building new therapies. Media and microbial procedures have been as described. All experiments during which cells have been released from a G1 arrest have been carried out by a issue arrest and release. The deg cin8 experiments had been carried out inside a similar manner, except that 2% galactose was additional to induce pGAL UBR1 thirty min prior to release ALK inhibitor into galactose at thirty C. Yeast strains are listed in Table S1. The deg cin8 construct was produced by PCR amplification with the to start with 600 bp with the CIN8 gene. The PCR fragment was digested with HindIII and XhoI and subcloned to the degron vector pPW66R to make an amino terminal fusion protein. The plasmid was linearized with Tth111I and integrated with the CIN8 locus. The ase1 5A plasmid was made by sequential website directed mutagenesis applying five various primers on plasmid pBB332 with the QuikChange Web site Directed Mutagenesis Kit from Stratagene.

For Ase1 overexpression, plasmid pSJ49 was linearized working with the Bst11071 enzyme and integrated with the TRP1 locus. All primer sequences are available upon request. Evaluation of Spc42 GFP, Spc29 GFP, and GFP Tub1 in fixed cells, or by dwell microscopy, had been performed as described. Indirect immunofluorescence was performed as described. Cells for EM were prepared by chemical Ribonucleic acid (RNA) fixation. Serial thin sections had been viewed on the JEOL 1010 electron microscope, and pictures were captured which has a Gatan digital camera. Photographs have been viewed with the Digital Micrograph Software package Package deal. Protein extracts have been produced and immunoblotted as described. 9E10 antibodies that realize the myc tag and 12CA5 antibodies that acknowledge the hemagglutinin tag have been obtained from Covance and made use of at a 1:ten,000 dilution.

M2 anti Flag antibodies that Dabrafenib price understand the Flag tag have been obtained from Sigma and employed at a 1:3000 dilution. Ase1 was detected using anti Ase1 antibodies at a one:500 dilution. Protein loading was confirmed in related experiments by anti tubulin immunoblotting. Cultures of mid log cells were collected, and lysates have been prepared and immunoprecipitated as described. For Ipl1 315 kinase assays, Ipl1 Flag or Ipl1 315 Flag was immunoprecipitated, as well as the beads were washed once and incubated with five mg recombinant histone H3 in kinase reactions as described. The reactions had been separated on SDS Page and subjected to autoradiography using a PhosphorImager Display. Kinase assays were quantified employing ImageQuant program.

For Ipl1 phosphorylation of Ase1, Ase1 myc was immunoprecipitated, plus the beads have been incubated with 5 mg of recombinant Ipl1 GST in kinase reactions as described.

In many experimental studies, induction of Cox 2 has been proven to promote cell growth and prevent apoptosis. Thus, inhibition of Cox 2 claims to be a successful strategy in preventing and treating cancer. In this review, Western blot analysis and RTPCR showed a specific loss of Cox 2 after BV therapy, while low inducible Cox 1 didn’t affect (-)-MK 801 any attention. These results might suggest that downregulation of Cox 2 inhibits induced apoptosis and cell growth. FasL is a type II transmembrane protein that plays a crucial role in immune homeostasis by presenting to the receptor Fas, a member of the cyst necrosis factor receptor superfamily, and inducing apoptosis. It’s recognized that the interaction between Fas and FasL activates caspase 8 and caspase 3, which leads to apoptosis. Thus, we examined whether BV causes up-regulation of Fas and FasL expression. As shown in Fig. 7B, BV treatment dramatically increased the degrees of Fas and FasL mRNA and protein more than 2 ug/ml at 48 h, suggesting that the results of BV in U937 are connected with Fas and FasL expression. The pieces comprising hTR, hTERT, Endosymbiotic theory telomerase and TEP 1, are essential determinants of telomerase activation. We therefore examined the changes in the mRNA expression in therapy with BV using RT PCR, to analyze the consequence of BV on a telomerase related gene. As shown in Fig. 7C, mRNA levels of hTERTalone considerably decreased, however not hTR and TEP 1, with therapy of BV in a dosedependent manner. In line with these results, more than 2 ug/ml led to a loss of the protein. These data may suggest that BV induces a decrease of telomerase activity through downregulation of hTERT. This time requires further study using apoptosisinducing inhibitors or overexpression of antiapoptotic protein, such as Bcl 2, in cancer cells, because mechanism of BV caused apoptosis, especially in leukemic ALK inhibitor cancer cells, has yet to be decided. Therefore, in the present research, we first examined how the apoptotic mechanismof BVwas assessed in human leukemic U937 cells. U937 cells treated with increased than 2 ug/ml showed a dose dependent inhibition of the growth, and cell shrinkage and nuclear condensation. Flow cytometric analysis also unveiled that BV therapy results in an increase of sub G1 DNA content, which is suggestive of apoptosis. These results suggest thatBV stimulated apoptosis contributes to the growth inhibition of U937 cells. Caspases, a family of cysteine proteases, are integrated parts of the apoptotic pathway, caspase 3 particularly, when activated, has several cellular targets that, when severed and/or activated, produce the morphologic characteristics of apoptosis.