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.
Affiliation
Department of Medicine, Program in Neuroscience, University of Massachusetts Medical School, 364 Plantation Street, Worcester, MA, 01605, USA.
Journal Details
This article was published in the following journal.
Name: Cellular and molecular neurobiology
ISSN: 1573-6830
Pages:
Links
- 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
Relaxation
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.
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