SMN Deficiency Reduces Cellular Ability to Form Stress Granules, Sensitizing Cells to Stress.
Summary of "SMN Deficiency Reduces Cellular Ability to Form Stress Granules, Sensitizing Cells to Stress."
Spinal Muscular Atrophy (SMA) is a neurodegenerative disease that is caused by deletion of the SMN (Survival of Motor Neuron) gene. The SMN protein is essential for cell survival and co-localized with TIA-1/R and G3BP, two characteristic markers of stress granules (SGs). To further study the SMN function in stress granules and in response to stress, we generated stable cell lines with SMN knockdown. Our data indicate that suppression of SMN drastically reduces cellular ability to form stress granules in response to stress treatment. In addition, we show that SMN deficiency sensitizes cells to sodium arsenite and H(2)O(2), two well-known stress inducers, leading to cell death at a much lower concentration of inducers in SMN knockdown cells than in control cells. Interestingly, the cell death is correlated with formation of stress granules, suggesting that involvement of SMN in formation of stress granules may play an important role in cell survival. Furthermore, rescue of SGs formation by overexpression of G3BP can reverse the defective formation of stress granules and results in partial abrogation of cell death against SMN deficiency. We deduce that modulation of stress response may be useful for potential SMN treatment.
Department of Medicine, Program in Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
This article was published in the following journal.
Name: Cellular and molecular neurobiology
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21234798
- DOI: http://dx.doi.org/10.1007/s10571-011-9647-8
Medical and Biotech [MESH] Definitions
Activity which reduces the feelings of tension and the effects of STRESS, PHYSIOLOGICAL.
Multiple Carboxylase Deficiency
A deficiency in the activities of biotin-dependent enzymes (propionyl-CoA carboxylase, methylcrotonyl-CoA carboxylase, and PYRUVATE CARBOXYLASE) due to one of two defects in BIOTIN metabolism. The neonatal form is due to HOLOCARBOXYLASE SYNTHETASE DEFICIENCY. The late-onset form is due to BIOTINIDASE DEFICIENCY.
Stress Disorders, Post-traumatic
A class of traumatic stress disorders with symptoms that last more than one month. There are various forms of post-traumatic stress disorder, depending on the time of onset and the duration of these stress symptoms. In the acute form, the duration of the symptoms is between 1 to 3 months. In the chronic form, symptoms last more than 3 months. With delayed onset, symptoms develop more than 6 months after the traumatic event.
Leukemia Virus, Feline
A species of GAMMARETROVIRUS causing leukemia, lymphosarcoma, immune deficiency, or other degenerative diseases in cats. Several cellular oncogenes confer on FeLV the ability to induce sarcomas (see also SARCOMA VIRUSES, FELINE).
Activating Transcription Factor 3
An activating transcription factor that plays a key role in cellular responses to GENOTOXIC STRESS and OXIDATIVE STRESS.
Eukaryotic cells respond to cellular stresses by the inhibition of translation and the accumulation of mRNAs in cytoplasmic RNA-protein (ribonucleoprotein) granules termed stress granules and P-bodies...
Mutations in fused in sarcoma (FUS) have been reported to cause a subset of familial amyotrophic lateral sclerosis (ALS) cases. Wild-type FUS is mostly localized in the nuclei of neurons, but the ALS...
The strong evolutionary conservation of the DNA methyltransferase, Dnmt2, is at odds with the absence of phenotypic defects in organisms lacking Dnmt2. The cellular processes where Dnmt2 has a role to...
P-bodies (processing bodies) are observed in different organisms such as yeast, Caenorhabditis elegans and mammals. A typical eukaryotic cell contains several types of spatially formed granules, such...
Mammalian cell cytoplasmic RNA stress granules are induced during various conditions of stress and are strongly associated with regulation of host mRNA translation. Several viruses induce stress granu...
Arimoclomol is a small molecule that upregulates "molecular chaperones" in cells under stress. Arimoclomol extends survival by five weeks when given both pre-symptomatically and at disease...
This study intends to study the efficacy and tolerability of once daily 3.0 g mesalazine granules vs. once daily 1.5 g mesalazine granules vs. three times daily 0.5 g mesalazine granules f...
The aim of the study is to explore the contribution of pollen starch granules to the induced symptoms and airway inflammation in patients with allergic rhinitis and mild asthma in a contro...
The purpose of this study is to determine whether bezafibrate is effective in the treatment of the muscular adult form of carnitine palmitoyltransferase 2 deficiency
Tuberculosis and vitamin D deficiency are important public health problems in India. Before the advent of effective antitubercular therapy, patients with tuberculosis were advised treatme...