Monday, February 9, 2009

Today is Stress Day! What are stress granules? What are Ceramides?!



So I just woke up at 4AM from a wonderful BIO dream. Study enough and you actually get BIO dreams! Well, this dream was terribly untrue, but it was a fascinating idea about how organisms use stress to adapt. No no no. I won't even write about the scientific heresy I dreamed up. But I have decided to declare today Stress day in that dreams honor! And today is Monday. I can't think of a better day for a stress day.

But first. A warning that the below is a product of 4am online searching and as you know, I am by no means a bio stress expert. We are both exploring this crazy jungle together remember? So take the below as a starting point for further exploration. :) Now go be stressful!

Short Text Clips:

This first text clip opened my eyes to STRESS GRANULES. Read below to find out more!

Viral Infection Affects Cell Stress Response
Link to Source
Release date: November 15, 2007 Source: Baylor College of Medicine
Viral infection disrupts the normal response of mammalian cells to outside deleterious forces, cleaving and inactivating a protein called G3BP that helps drive the formation of stress granules, which shelter the messenger RNAs that carry the code for protein formation, said researchers from Baylor College of Medicine in Houston. Only recently have scientists begun to understand the role of stress granules, said Dr. Richard Lloyd, associate professor of molecular virology and microbiology at BCM, and senior author of the report that appears today in the journal Cell Host and Microbe. The stress granules are formed when a cell is subjected to several kinds of stress, such as nutrient deprivation or virus infection. "When the cell suffers a major insult, it stops expanding. The business of protein synthesis (in which messenger RNA or mRNA's genetic code gets translated into proteins that carry out cellular activities) is arrested. The messenger RNA goes into storage until conditions improve for the cells," he said. "Stress granules are a major storage site for the mRNA." However, in poliovirus infection (used in the laboratory because it is a prototype for many kinds of viruses), the stress granules are formed early but as the infection continues, the stress granules disperse. Lloyd and his colleagues found that the poliovirus infection actually cuts or cleaves G3BP, a protein critical in the formation of the stress granules.

Link to Wiki:
Stress Granules
Stress granules are dense aggregations in the cytosol composed of proteins & RNAs that appear when the cell is under stress. The RNA molecules stored are stalled translation pre-initiation complexes - failed attempts to make protein from mRNA. Stress granules are 100-200nm in size, not surrounded by membrane, and associated with the endoplasmatic reticulum.[1] Note that there are also nuclear stress granules. This article is about the cytosolic variety.The purpose of stress granules might be to protect RNAs from harmful conditions, thus their appearance under stress.[2] The accumulation of RNAs into dense globules could keep them from reacting with harmful chemicals and safe-guard the information coded in their RNA sequence. Stress granules might also function as a decision point for untranslated mRNAs. Molecules can go down one of three paths: further storage, degradation, or re-initiation of translation. The stress proteins that are the main component of stress granules in plant cells are molecular chaperones that sequester, protect, and possibly repair proteins that unfold during heat and other types of stress.[4][5] Therefore any association of mRNAs with stress granules may simply be a side effect of the association of partially unfolded RNA-binding proteins with stress granules,[6] similar to the association of mRNAs with proteasomes.[7]

This next text clip introduced me to Ceramides!

Ceramides as Key Players in Cellular Stress Response (2000) FULL TEXT FREE
The recent discovery of sphingolipid-derived second messengers that regulate fundamental cell responses such as cell growth and apoptosis has provided insight into the way cells sense and respond to stressful stimuli. This will help the understanding of the pathogenesis of stress-related diseases and eventually offer novel therapeutic approaches.

LINK TO WIKI: Ceramides

Ceramides are a family of lipid molecules. A ceramide is composed of sphingosine and a fatty acid. Ceramides are found in high concentrations within the cell membrane of cells. They are one of the component lipids that make up sphingomyelin, one of the major lipids in the lipid bilayer. For years, it was assumed that ceramides and other sphingolipids found in the bilayer cell membrane were purely structural elements. This is now known to be not completely true. Perhaps one of the most fascinating aspects of ceramide is that it can act as a signaling molecule. The most well-known functions of ceramides as cellular signals include regulating the differentiation, proliferation, programmed cell death (PCD), and apoptosis (Type I PCD) of cells.What's the Physiological Roles of Ceramide? As a bioactive lipid, ceramide has been implicated in a variety of physiological functions including apoptosis, cell growth arrest, differentiation, cell senescence, cell migration and adhesion. [2] Roles for ceramide and its downstream metabolites have also been suggested in a number of pathological states including cancer, neurodegeneration, diabetes, microbial pathogenesis, obesity, and inflammation. [4]


More: Full Text Open Access to other Research Papers Related to Stress:

Genomic expression programs of human cell lines in response to physiological stress (2000)
"In a previous study of gene expression, the yeast Saccharomyces cerevisiae was shown to change its gene expression dramatically in response to a wide variety of stresses1. The large transcriptional response, which is activated in response to a wide variety of stresses., consists of over 1000 genes. This response, termed the environmental or general stress response, which has not yet been observed in human cells, is likely to have evolved to allow the yeast to survive the wide variety of environmental conditions it is exposed to in the course of its natural existence. Human cells in vivo are not subjected to the wide variety of environmental conditions seen by a unicellular organism such as yeast. In addition, mammalian cells have physiological responses to stress that are entirely absent in yeast, for example apoptosis and changes in cell-cell interactions. We might therefore expect the stress-induced changes in gene expression in mammalian cells to differ from those observed in yeast. Transcriptional systems used by mammalian cells in response to stress are also interesting because of their potential roles in human diseases. For instance, many human diseases, including most cancers, are characterized by a reduced ability of cells to respond to certain stresses. In order to characterize the mammalian stress response, we have measured gene expression under a diverse set of conditions including oxidative stress, exposure to ultraviolet light, crowding and starvation, cold, heat and denaturing extracellular conditions in HeLa S3 cervical carcinoma cells."

Bone cell responses to high-frequency vibration stress: does the nucleus oscillate within the cytoplasm? (2006)

REGULATION OF THE ADRENOCORTICOTROPHIN RESPONSE TO STRESS BY THE CENTRAL NUCLEUS OF THE AMYGDALA IN RATS DEPENDS UPON THE NATURE OF THE STRESSOR 1996

Ceramides and sphingomyelins in skeletal muscles of the rat: content and composition. Effect of prolonged exercise 2002
"The sphingomyelin-signaling pathway has been described in many tissues. Ceramide is the main second messenger in this pathway."

Proteomic Analysis of Cellular Response to Osmotic Stress in Thick Ascending Limb of Henle’s Loop (TALH) Cells*


Stress granules: sites of mRNA triage that regulate mRNA stability and translatability (2002)

The biophysics of ceramides and related simple sphingolipids. 18 June 2008
"Sphingolipids were named after the Egyptian sphinx, a dicotomic sculpture with a human head attached to a lion’s body. In 1884, J.L.W. Thudichum described a group of lipids with a polar “head” attached to a hydrophobic “body.” The simplest sphingolipids are sphingosine ((2S,3R,4E)-2-amino-4-octadecene-1,3-diol) (Sph) and ceramide (N-acylsphingosine) (Cer), which are the scaffold of other more complex sphingolipids such as sphingomyelin (SM) and glycosphingolipids. Initially, sphingolipids were considered as mere structural lipids in biological membranes or just intermediates in the metabolism of other lipids. Two decades ago, some studies started to elucidate that sphingolipids are also involved in signaling pathways which range from cell proliferation and survival to cell senescence and apoptosis...."

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