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| SPOTLIGHTS ON NEW PUBLICATIONS |
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| Year : 2014 | Volume
: 7
| Issue : 1 | Page : 75-76 |
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Spotlights on new publications
Sherif M Abaza
Department of Parasitology, Faculty of Medicine, Suez Canal University, Suez, Egypt
| Date of Submission | 01-Jun-2014 |
| Date of Acceptance | 11-Jun-2014 |
| Date of Web Publication | 25-Sep-2014 |
Correspondence Address:
Sherif M Abaza
PhD, Department of Parasitology, Faculty of Medicine, Suez Canal University, Suez
Egypt
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1687-7942.139694
How to cite this article:
Abaza SM. Spotlights on new publications. Parasitol United J 2014;7:75-6 |
Apoptosis is a form of programmed cell death, and its signs have been recognized in parasites such as the kinetoplastids, apicomplexans, amoebozoa, trichomonads, diplomonads, and Blastocystis spp., suggesting an ancient origin of death-regulating genes during the evolution of eukaryotes. Apoptosis hallmarks in these organisms include shrinkage and cell rounding-up, externalization of phosphatidylserine from the inner to the outer cell membrane leaflet while maintaining membrane integrity, DNA fragmentation, and chromatin condensation. Cysteine peptidases with specificity for aspartate (caspases) are key players of apoptosis, which makes them promising targets for the development of novel intervention strategies against parasites of medical and veterinary importance. Caspases, a family of cysteine proteases, are of three types: apoptosis initiators, apoptosis executioners, and inflammatory mediators. The second type (executioner) includes caspases 3, 6, 7, and 14, and they remain in dimeric forms even in the inactive state. On the contrary, the first type (initiators) including caspases 2, 8, 9, and 10, as well as the inflammatory mediators including caspases 1, 4, 5, 9, 11, 12, and 13, form dimers in specific conditions or remain as monomers in the cytosol.
In the present issue, the induction of apoptosis as one of the most promising strategies for drug development against parasitic diseases with high morbidity and mortality, such as schistosomiasis and cerebral malaria (CM), will be compiled and summarized.
Schistosomiasis: The executioner caspases 3 and 7 exist within the cytosol as inactive dimers and are activated by dimerization. Generally speaking, phylogenetic studies of caspases from worms considered to be of a primitive order, such as flukes, revealed that they are highly diverse and different from those of their mammalian hosts. Hence, Shakti Kumar and his colleagues hypothesized that caspases 3 and 7 of blood flukes may emerge as potent drug targets against schistosomiasis. They analyzed the interacting domains of caspases 3 and 7 of Schistosoma spp. at the sequence and structural levels and performed the protein-protein docking for studying their geometrical arrangement in the dimer state. Sequences of caspases 3 and 7 from Schistosoma mansoni and Schistosoma japonicum as well as from human were retrieved from GenBank and protein-protein docking simulation was performed to reveal differences between the host-parasite systems. Caspase-3 sequences of both schistosomes shared 70% similarity between themselves. However, the two available caspase-7 sequences of S. mansoni surprisingly shared only 19% identity to each other, despite belonging to the same species. On the contrary, in human caspases, there is higher percentage of aromatic, hydrophilic, and positively and negatively charged amino acids as compared with those in schistosomal caspases. The investigators concluded that Schistosoma spp. caspases 3 and 7 are homologs of human caspases. The schistosomal caspases are unique in comparison with those of their host in two main points: (a) At the secondary structure level, the schistosomal caspase active sites have different secondary structural elements (combination of β-sheets and coils) and these structural differences may affect their protease activity. (b) In the schistosomal caspases also, there is a large cavity with a rough surface formed because of the occurrence of a large number of small amino acids at the dimer interface. This cavity may be responsible for adopting different dimer conformation structures during the protein-protein docking simulation, resulting in reduction in the dimer stability, and thereby affecting apoptosis initialization. Thus, the parasite executioner caspases may be exploited as potent drug targets of chemotherapeutic use.
In-silico analysis of caspase-3 and -7 proteases from blood-parasitic Schistosoma species (Trematoda) and their human host. Bioinformation 2013; 9:456-463.
Malaria: CM is associated with the sequestration of parasitized red blood cells (PRBCs) in the microvasculature and the release of soluble cytokines. An important signaling factor, nuclear factor-κB (NF-κB) is known to regulate apoptosis. Chuchard Punsawad and his colleagues aimed to investigate NF-κB p65 activation and its involvement in caspase-3 expression and its correlation with brain apoptosis of fatal CM. The correlation between NF-κB p65 and caspase-3 expression was analyzed using clinical and histopathologic parameters. Brain tissues from CM patients and normal brain tissues were obtained from patients who had died of accidents without head injury. The brain tissues were stained for histopathologic studies, whereas the immunohistochemical studies were conducted for the correlation between NF-κB p65 and cleaved caspase 3. Known positive controls (breast cancer for NF-κB p65 and lymph node for cleaved caspase 3) were used to confirm the specificity of primary antibodies and to validate the immunohistochemical-staining techniques. The quantitative NF-κB p65 immunoreactivity was evaluated in NF-κB p65-stained cells. Cleaved caspase 3 stained with red color in the cytoplasm and/or nucleus of a cell was considered an apoptotic cell. For the histopathologic changes in the brain of CM and non-CM patients, results showed that the mean total score in the first group was 4.4 points, whereas no significant histopathologic changes were observed in the second group. Localized NF-κB p65 immunostaining was detected in the cytoplasm and/or nucleus of cellular components in the neurons, glial cells, as well as intravascular leukocytes. Of the vascular endothelial cells (ECs), targets of PRBC cytoadhesion, 60% were immunopositive for NF-κB p65 as compared with ˜30% in the control group, with statistical significant difference. In addition, intravascular lymphocytes showed higher nuclear immunoreactivity against NF-κB p65 than the control and non-CM group, indicating the active state of these cells during malaria infection. Glial cells and neurons of the CM group exhibited radial immunostaining of cleaved caspase 3 (resembling a spider-web pattern), while there was no detectable cleaved caspase-3 immunoreactivity in the brains of the control group. In addition, ECs immunopositive for activated caspase 3 were observed in the blood vessels containing PRBC sequestration, as well as both circulating and adherent leukocytes. The percent of ECs immunopositive for cleaved caspase 3 was significantly increased in the CM group compared with the non-CM group. Finally, the percentage of neurons that expressed NF-κB p65 correlated positively with the total score for histopathologic changes. There was a significant positive correlation between nuclear ECs NF-κB index and ECs apoptotic index, and between intravascular leukocyte NF-κB index and leukocyte apoptotic index in the CM group. It was concluded from the study that the activation of NF-κB p65 and apoptosis was established in the neurons, glial cells, ECs, and intravascular leukocytes of CM patients. In addition, it demonstrated that NF-κB is one of the signaling molecules that modulate apoptosis of ECs and intravascular leukocytes of fatal CM.
Nuclear factor kappa B modulates apoptosis in the brain endothelial cells and intravascular leukocytes of fatal cerebral malaria. Malar J 2013; 12:260.
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