Role of Apoptosis in disease

Dipartimento di Scienze Biomediche, Universita' "G. d'Annunzio" Chieti-Pescara, Italy.
Aging (Impact Factor: 6.43). 05/2012; 4(5):330-49.
Source: PubMed


Since the initial description of apoptosis, a number of different forms of cell death have been described. In this review we will focus on classic caspase-dependent apoptosis and its variations that contribute to diseases. Over fifty years of research have clarified molecular mechanisms involved in apoptotic signaling as well and shown that alterations of these pathways lead to human diseases. Indeed both reduced and increased apoptosis can result in pathology. More recently these findings have led to the development of therapeutic approaches based on regulation of apoptosis, some of which are in clinical trials or have entered medical practice.

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    • "The control or any disorder in it has the effective role in malignant deformation process, cancer progress and metastases (Bold et al., 1997; Kamesaki et al., 1998). Apoptosis is done through two different pathways including the death-receptor pathway and mitochondrial pathway (Favaloro al., 2012). The B-cell lymphoma 2 (Bcl-2) family represents apoptosis regulating proteins integrating diverse intra-and extracellularly generated survival and death signals. "
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    ABSTRACT: Gastric cancer accounts for about 8% of the total cancer cases and 10% of total cancer deaths worldwide. It is the second lethal cancer after esophageal cancer and is considered the fourth most common cancer in north and northwest Iran. The bcl2 family has a key role in the regulation of apoptosis and change in its expression can contribute to cancer. This study initially scheduled to determine the expression of bcl2 gene in tissue samples of adenocarcinoma cancer patients. A total of 10 samples of gastric adenocarcinoma and 10 of normal tissues from Sari hospital were selected and after DNA extraction from tissues, bcl2 gene expression assayed by real-time PCR. Our results demonstrated higher expression of the bcl2 gene in control compared with cancer and marginal cancer tissues. On one hand BCL2 plays an important role as an oncogene to inhibit apoptosis; on the other hand, it can initiate cell cycle arrest at G0 stage. Our observed association between its expression and patient survival is quite conflicting and may be tissue-specific. The data suggest expression both tumoural and non-tumoral(marginal) groups have lowered expression than controls (P>0.05). Due to the low number of samples we could not examine the relationship with clinicopathological features. However, bcl-2 expression may be important for prognostic outcome or a useful target for therapeutic intervention.
    Asian Pacific journal of cancer prevention: APJCP 08/2015; 16(14):6067-71. DOI:10.7314/APJCP.2015.16.14.6067 · 2.51 Impact Factor
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    • "With apoptosis, there exists an early phase that consists of the loss of plasma membrane lipid phosphatidylserine asymmetry that can identify cells for disposal by microglia in the nervous system (Schutters and Reutelingsperger, 2010; Wei et al., 2013; Williams and Dexter, 2014). A later phase in apoptosis results in cell death with DNA degradation (Chong et al., 2005b, 2006; Favaloro et al., 2012; Folch et al., 2012; Shao et al., 2013; Nguyen et al., 2014). During DM, apoptosis results in the death of neurons (Das et al., 2011; Aksu et al., 2012; Kimura et al., 2013; Mao et al., 2014), pancreatic β-cell loss (Deng et al., 2009; Choi et al., 2010; Miao et al., 2013), and endothelial cell destruction (Chong et al., 2007; Hou et al., 2010b; Hamed et al., 2011; Chen et al., 2012; Arunachalam et al., 2014). "
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    ABSTRACT: Diabetes mellitus affects almost 350 million individuals throughout the globe resulting in significant morbidity and mortality. Of further concern is the growing population of individuals that remain undiagnosed but are susceptible to the detrimental outcomes of this disorder. Diabetes mellitus leads to multiple complications in the central and peripheral nervous systems that include cognitive impairment, retinal disease, neuropsychiatric disease, cerebral ischemia, and peripheral nerve degeneration. Although multiple strategies are being considered, novel targeting of trophic factors, Wnt signaling, Wnt1 inducible signaling pathway protein 1, and stem cell tissue regeneration are considered to be exciting prospects to overcome the cellular mechanisms that lead to neuronal injury in diabetes mellitus involving oxidative stress, apoptosis, and autophagy. Pathways that involve insulin-like growth factor-1, fibroblast growth factor, epidermal growth factor, and erythropoietin can govern glucose homeostasis and are intimately tied to Wnt signaling that involves Wnt1 and Wnt1 inducible signaling pathway protein 1 (CCN4) to foster control over stem cell proliferation, wound repair, cognitive decline, β-cell proliferation, vascular regeneration, and programmed cell death. Ultimately, cellular metabolism through Wnt signaling is driven by primary metabolic pathways of the mechanistic target of rapamycin and AMP activated protein kinase. These pathways offer precise biological control of cellular metabolism, but are exquisitely sensitive to the different components of Wnt signaling. As a result, unexpected clinical outcomes can ensue and therefore demand careful translation of the mechanisms that govern neural repair and regeneration in diabetes mellitus.
    Neural Regeneration Research 04/2015; 10(4):518-528. DOI:10.4103/1673-5374.155427 · 0.22 Impact Factor
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    • "Several possibilities are discussed. Survivin seems to exert its activity through the inhibition of caspase activities (Zaffaroni et al., 2005; Adamkov et al., 2009b; Favaloro et al., 2012). Caspases can be inactivated either by overexpression of endogenous caspase inhibitors, by direct mutations within the caspase coding genes or by silencing of the corresponding promoters via methylation (Jones, 2001; Angell, 2008). "
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    ABSTRACT: Mismatch repair genes (MMR) play an essential role in DNA repair. MMR mutations predominantly in MLH1, MSH2, MSH6, PMS2, and rarely in PMS1, may cause the production of abnormally short or inactivated proteins. The antiapoptotic protein survivin functions in the inhibition of apoptosis, regulation of cell division and also enhances angiogenesis. Both MMRP and survivin are considered to be powerful prognostic parameters. This study was designed to determine the relationship between MMRP and survivin in colon lesions. The study included 113 cases of colon carcinoma and 51 cases of colon polyps. Survivin expression and MMRP status were assessed by immunohistochemistry. In each section, expression, intensity of immunostaining and percentage of labeled cells were analyzed. In carcinomas, immunoreaction was detected in 100/113 cases for MLH1 (88.5%), 112/113 cases for MSH2 (99.1%), 110/113 cases for MSH6 (97.3%), and 103/113 cases for PMS2 (91.2%). Survivin was shown in 47/113 cases (41.6%). The statistical analysis confirmed a significant correlation between the expression of MMRP and survivin in the assessed parameters. All 51 polyp samples were positive for MLH1, MSH2, MSH6 and PMS2. Only 8 of those (15.7%) were positive for survivin. Statistically significant differences were observed between the expression of MMRP and survivin. In conclusion, this study revealed that MMRP may suppress the antiapoptotic function of survivin through p53 inactivation of its promoter in grade 1 and grade 2 colon carcinomas.
    Acta histochemica 05/2014; DOI:10.1016/j.acthis.2014.04.005. · 1.71 Impact Factor
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