Role of cited-1 and caspase-6 expression in HELLP syndrome.

OBJECTIVE: In this study, we investigated the immunohistochemical staining of cited-1 and caspase-6 expression in the placentas of pregnant women with HELLP syndrome. PATIENTS AND METHODS: Placentas of 20 normotensive patients and 20 women with HELLP syndrome were processed for routine histological tissue processing. The biochemical and clinical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and cited-1 and caspase-6 immunostaining. RESULTS: Placentas of normotensive patients showed normal histology. Placentas of women with HELLP syndrome showed degenerated cells, hyalinization and vacuolization. Cited-1 expression was negative in normotensive group; however, it was increased in HELLP group, especially in decidual cells, endothelial cells and other placental cells. Caspase-6 expression was negative in placental structures of normotensive groups. However, it was intense in decidual cells, vacuolar and hyalinized areas, inflammatory cells and connective tissue cells in HELLP group. CONCLUSIONS: Cited-1 and caspase-6 are a marker in determining the severity of HELLP syndrome.

The effectiveness of different neuroprotective agents in facial nerve injury: An experimental study.

OBJECTIVES/HYPOTHESIS: To examine and compare the neuroprotective effects of dexamethasone, oxytocin, and resveratrol administration on regeneration after facial nerve crush injury in a rat model. STUDY DESIGN: Prospective, randomized, controlled animal study. METHODS: A crush-type facial nerve injury was performed on the right side of all rats (injury group [IG]), whereas there was no injury on the left side (sham group [SG]). These main groups were divided into five subgroups: 1) no medicine (control); 2) physiological serum; 3) dexamethasone; 4) oxytocin; and 5) resveratrol (Res) administered (intraperitoneal injection) for 28 days. Functional recovery was evaluated by daily eye-blink reflex and facial electromyography. Nerve-muscle degeneration and regeneration, apoptosis, and intercellular connections were evaluated in histopathological and immunohistochemical examinations. RESULTS: Recovery time of the postinjury eye-blink reflex demonstrated faster recovery in IG+Res when compared with the other subgroups. In peak-to-peak amplitude values, a significant increase was observed in the dexamethasone (P=0.007) and oxytocin subgroups (P=0.004) and was even more apparent in the resveratrol subgroup (P<0.001). Nerve regeneration is apparent in the resveratrol subgroup. Apoptotic changes were evaluated immunohistochemically with TUNEL and Caspase 3 and 6 antibodies staining. Caspase 3 and 6 immunoexpressions of resveratrol and oxytocin subgroups were moderate when compared with dexamethasone subgroup. Except for the resveratrol subgroup, which had an increase in expression, the majority of subgroups were similar to SG in terms of intercellular connections (Connexin 32 and 43). CONCLUSION: Resveratrol leads to the best outcome after facial nerve crush injury in rats when compared with dexamethasone and oxytocin, even though these agents demonstrate a significant improvement in facial nerve regeneration. LEVEL OF EVIDENCE: N/A.

A comprehensive characterization of the caspase gene family in insects from the order Lepidoptera.

BACKGROUND: The cell suicide pathway of apoptosis is a necessary event in the life of multicellular organisms. It is involved in many biological processes ranging from development to the immune response. Evolutionarily conserved proteases, called caspases, play a central role in regulating apoptosis. Reception of death stimuli triggers the activation of initiator caspases, which in turn activate the effector caspases. In Lepidoptera, apoptosis is crucial in processes such as metamorphosis or defending against baculovirus infection. The discovery of p35, a baculovirus protein inhibiting caspase activity, has led to the characterization of the first lepidopteran caspase, Sf-Caspase-1. Studies on Sf-Caspase-1 mode of activation suggested that apoptosis in Lepidoptera requires a cascade of caspase activation, as demonstrated in many other species. RESULTS: In order to get insights into this gene family in Lepidoptera, we performed an extensive survey of lepidopteran-derived EST datasets. We identified 66 sequences distributed among 27 species encoding putative caspases. Phylogenetic analyses showed that Lepidoptera possess at least 5 caspases, for which we propose a unified nomenclature. According to homology to their Drosophila counterparts and their primary structure, we determined that Lep-Caspase-1, -2 and -3 are putative effector caspases, whereas Lep-Caspase-5 and -6 are putative initiators. The likely function of Lep-Caspase-4 remains unclear. Lep-Caspase-2 is absent from the silkworm genome and appears to be noctuid-specific, and to have arisen from a tandem duplication of the Caspase-1 gene. In the tobacco hawkmoth, 3 distinct transcripts encoding putative Caspase-4 were identified, suggesting at least 2 duplication events in this species. CONCLUSIONS: The basic repertoire of five major types of caspases shared among Lepidoptera seems to be smaller than for most other groups studied to date, but gene duplication still plays a role in lineage-specific increases in diversity, just as in Diptera and mammals.

Expression analysis of caspase-6, caspase-9 and BNIP3 in prostate cancer.

AIMS: Altered regulation of cell death is a feature of human cancer. The aim of this study was to explore whether the expression of the proapoptotic proteins caspase-6, caspase-9, and Bcl-2/adenovirus E1B-19kDa-interacting protein3 (BNIP3) is altered in prostate cancers. METHODS: We analyzed the expression of caspase-6, caspase-9, and BNIP3 in 107 prostate adenocarcinoma tissues by immunohistochemistry using a tissue microarray (TMA) method. RESULTS: Normal glandular cells expressed caspase-6 and BNIP3 proteins in 10 (9.3%) and 9 (8.4%) prostate tissues, respectively. By contrast, the prostate cancers expressed caspase-6 and BNIP3 in 65 (60.7%) and 69 (64.5%) cases, respectively. Prostate intraepithelial neoplasia (PIN) showed caspase-6 and BNIP3 expression in 65% and 65% of cases, respectively. We observed caspase-9 expression in 40 (37.4%) normal, 8 (40%) PIN, and 45 (42.1%) cancer tissues. None of the expression of caspase-6, caspase-9 or BNIP3 was associated with pathological characteristics such as tumor size, patient age, Gleason score, or tumor stage. CONCLUSION: Our data showed that prostate cancer and PIN cells display higher expression of the proapoptotic proteins caspase-6 and BNIP3 than normal cells. Neo-expression of these proteins from the PIN stage suggests that apoptosis deregulation might occur in the early stage of prostate carcinogenesis, and that altered expression of proapoptotic proteins may be a feature of prostate cancer.

Intestinal cellular localization of PCNA protein and CYP1A mRNA in Atlantic salmon Salmo salar L. exposed to a model toxicant.

BACKGROUND: The aim of the study was to examine the intestinal cellular localization of proliferating cell nuclear antigen (PCNA) and cytochrome P450 A1 (CYP1A) expression in Atlantic salmon Salmo salar L. exposed to a model toxicant. The stress response was induced by intraperitoneal injection of four salmon with a single dose (50 mg/kg) of the CYP1A inducer beta-naphthoflavone (BNF) and intestinal tissue (mid and distal intestine; MI and DI) was sampled seven days later. Samples for histology and gene transcription analysis were collected from four exposed fish and four control fish. PCNA was assessed by immunohistochemistry, CYP1A mRNA was studied by in situ hybridization (ISH) and finally the transcription of five genes was quantified by real-time quantitative RT-PCR (real-time RT-PCR); two detoxifying genes (CYP1A and glutathione S-transferase; GST), a stress marker gene (heat shock protein 70; HSP70), PCNA and a gene marker of apoptosis (caspase 6A). RESULTS: PCNA protein and CYP1A mRNA were successfully localized in the intestinal cells (MI) of both experimental groups. At the cellular level, BNF significantly lowered intestinal cell proliferation and increased the CYP1A mRNA levels compared to the control group. The real-time RT-PCR data, which showed an increased mRNA expression both in the MI and DI of 139- and 62-fold, respectively, confirmed the increased cellular CYP1A mRNA levels detected using ISH. HSP70 expression was also up-regulated in the exposed fish. The other examined genes did not show any differential regulation in the experimental fish group. CONCLUSION: This study showed that CYP1A mRNA had a specific intestinal cellular transcription pattern in Atlantic salmon exposed to BNF. At the cellular level CYP1A mRNA expression was always observed at or around the cell nucleus close to the basolateral cell membrane and at the tissue level CYP1A mRNA expression was most frequently observed in the basal and apex area of the intestinal folds. Taken together, a link between the intestinal detoxification system (CYP1A) and cell renewal system (PCNA) is indicated with these two processes being inversely correlated in BNF exposed fish.

Co-localization of hyperphosphorylated tau and caspases in the brainstem of Alzheimer's disease patients.

Hyperphosphorylation of microtubule associated protein tau had limited studies in Alzheimer's disease (AD) brainstem. We compared the distribution and number of neurons with hyperphosphorylated tau in two age groups of AD brainstems with mean ages of 65.4 +/- 5.7 and 91.1 +/- 6.4 years. The degree of co-localization of hyperphosphorylated tau positive cells with either cleaved caspase-3 or cleaved caspase-6 was also quantified. Results showed hyperphosphorylated tau mainly occurred in hypoglossal, dorsal motor vagal, trigeminal sensory/motor nuclei as well as in dorsal raphe, locus coeruleus and substantia nigra. Older AD brainstem consistently had higher density of hyperphosphorylated tau cells. Up to 70% of tau positive cells also displayed either cleaved caspase-3 or caspase-6, and the number of co-localized tau cells in each caspase subfamily group was always higher in older aged group. Some hyperphosphorylated tau cells with cleaved caspases had TUNEL positive nuclei. These findings suggest that these latter cells went through the apoptotic process or DNA fragmentation.