Defects in genes encoding ribosomal proteins cause Diamond Blackfan Anemia (DBA), a red cell aplasia often associated with physical abnormalities. Other bone marrow failure syndromes have been attributed to defects in ribosomal components but the link between erythropoiesis and the ribosome remains to be fully defined. Several lines of evidence suggest that defects in ribosome synthesis lead to "ribosomal stress" with p53 activation and either cell cycle arrest or induction of apoptosis. Pathways independent of p53 have also been proposed to play a role in DBA pathogenesis. We took an unbiased approach to identify p53-independent pathways activated by defects in ribosome synthesis by analyzing global gene expression in various cellular models of DBA. Ranking-Principal Component Analysis (Ranking-PCA) was applied to the identified datasets to determine whether there are common sets of genes whose expression is altered in these different cellular models. We observed consistent changes in the expression of genes involved in cellular amino acid metabolic process, negative regulation of cell proliferation and cell redox homeostasis. These data indicate that cells respond to defects in ribosome synthesis by changing the level of expression of a limited subset of genes involved in critical cellular processes. Moreover, our data support a role for p53-independent pathways in the pathophysiology of DBA.
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http://dx.doi.org/10.1016/j.gene.2014.04.077 | DOI Listing |
Genes (Basel)
November 2024
School of Neurobiology, Biochemistry and Biophysics, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 6997801, Israel.
The human mitochondrial proteome comprises approximately 1500 proteins, with only 13 being encoded by mitochondrial DNA. The remainder are encoded by the nuclear genome, translated by cytosolic ribosomes, and subsequently imported into and sorted within mitochondria. The process of mitochondria-destined protein import is mediated by several intricate protein complexes distributed among the four mitochondrial compartments.
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December 2024
Department of Psychiatry, University of Iowa, Carver College of Medicine, Iowa City, IA, 52242, USA.
Maternal stress during pregnancy, or prenatal stress, is a risk factor for neurodevelopmental disorders in offspring, including autism spectrum disorder (ASD). In ASD, dorsal striatum displays abnormalities correlating with symptom severity, but there is a gap in knowledge about dorsal striatal cellular and molecular mechanisms that may contribute. Using a mouse model, we investigated how prenatal stress impacted striatal-dependent behavior in adult offspring.
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December 2024
Laboratorio de Medicina Experimental, Hospital Alemán, Av. Pueyrredón 1640, C1118AAT, Ciudad Autónoma de Buenos Aires, Argentina.
Chronic hypertension is an increasingly prevalent condition that constitutes a risk factor for superimposed preeclampsia during pregnancy. In this study, we assessed the gut microbiome in a rat model of superimposed preeclampsia to characterize the microbial signature associated with defective placentation processes identified at the preclinical disease stage. The blood pressure profile, renal function parameters and fetal phenotype were evaluated in pregnant Stroke-prone Spontaneously Hypertensive Rats (SHRSP) and their normotensive controls.
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December 2024
Department of Orthopaedic Surgery, CHA Bundang Medical Center, CHA University School of Medicine, 335 Pangyo-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13488, Republic of Korea.
Articular cartilage has a limited regenerative capacity, resulting in poor spontaneous healing of damaged tissue. Despite various scientific efforts to enhance cartilage repair, no single method has yielded satisfactory results. With rising drug development costs, drug repositioning has emerged as a viable alternative.
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December 2024
Center for Oral Health Research, College of Dentistry, University of Kentucky, Lexington, KY, USA.
Type 2 diabetes mellitus (T2DM) is associated with cellular abnormalities, tissue and organ dysfunctions, and periodontitis. This investigation examined the relationship between the oral microbiome and salivary biomarkers in T2DM patients with or without periodontitis. This cohort (35-80 years) included systemically healthy non-periodontitis (NP; n = 31), T2DM without periodontitis (DWoP; n = 32) and T2DM with periodontitis (DWP; n = 29).
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