Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Sept 10, 2011 23:20:47 GMT -5
www.ncbi.nlm.nih.gov/pubmed/11503418?dopt=AbstractJ Toxicol Environ Health B Crit Rev. 2001 Jul-Sep;4(3):313-32. Biomarkers of apoptosis: release of cytochrome c, activation of caspase-3, induction of 8-hydroxy-2'-deoxyguanosine, increased 3-nitrotyrosine, and alteration of p53 gene.Abu-Qare AW, Abou-Donia MB. Abstract Biomarkers rely on biochemical, histological, morphological, and physiological changes in whole organisms. Their use is becoming an important tool to examine changes at cellular and molecular levels, especially in nucleic acids and proteins. Biomarkers are used to measure exposure to a toxic agent, to detect severity of any toxic response, and to predict the possible outcome. Information on the mechanisms of action of toxicants can allow the development of potential biomarkers of effect and thus improvement of the risk assessment processes. Use of biomarkers as a tool to predict induction of apoptosis allows identification of biological signs that may indicate increased risk for disease. In cells undergoing apoptosis, the release of cytochrome c from the mitochondria to the cytoplasm and the activation of caspase-3, a key enzyme to execution stage of apoptotic pathway, have been studied as biomarkers of cell death (apoptosis). Products of DNA fragmentation that either accumulate in the cellular tissues or are excreted in the urine are useful markers of DNA damage. The induction level of urinary or cellular level of 8-hydroxy-2-deoxyguanosine and 3-nitrotyrosine has been used as a marker to measure extent of DNA oxidative damage. Furthermore, alteration or overexpression of the p53 gene was considered an indication of apoptosis. This article reviews some of the aspects of biomarkers of apoptosis, indicating relevance of their uses to predict apoptosis following exposure to environmental toxicants. PMID: 11503418
|
|
|
Post by beebs on Sept 11, 2011 17:40:45 GMT -5
Anyone did relevant tests as mentioned in this article?
|
|
Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Sept 13, 2011 7:20:10 GMT -5
Hi Beebs, I am writing now from memory. Caspase 3 plays a central role in the execution-phase of cell apoptosis (programmed cell death) nitrotyrosin is a product mediated by reactive nitrogen species like NO (nitric oxdie,) ONOO (peroxynitrite) - In my country this is a normal test in a lab. p53 gene - important role in apoptosis 8-hydroxy-2'-deoxyguanosine - measurement of oxidative stress. en.wikipedia.org/wiki/Cytochrome_cCytochrome c is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in calcium levels precedes cyt c release from the mitochondria. The release of small amounts of cyt c leads to an interaction with the IP3 receptor (IP3R) on the endoplasmic reticulum (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within.
|
|
|
Post by beebs on Sept 15, 2011 3:36:37 GMT -5
Hi Beebs, I am writing now from memory. Caspase 3 plays a central role in the execution-phase of cell apoptosis (programmed cell death) nitrotyrosin is a product mediated by reactive nitrogen species like NO (nitric oxdie,) ONOO (peroxynitrite) - In my country this is a normal test in a lab. p53 gene - important role in apoptosis 8-hydroxy-2'-deoxyguanosine - measurement of oxidative stress. en.wikipedia.org/wiki/Cytochrome_cCytochrome c is released by the mitochondria in response to pro-apoptotic stimuli. The sustained elevation in calcium levels precedes cyt c release from the mitochondria. The release of small amounts of cyt c leads to an interaction with the IP3 receptor (IP3R) on the endoplasmic reticulum (ER), causing ER calcium release. The overall increase in calcium triggers a massive release of cyt c, which then acts in the positive feedback loop to maintain ER calcium release through the IP3Rs. This explains how the ER calcium release can reach cytotoxic levels. This release of cytochrome c in turn activates caspase 9, a cysteine protease. Caspase 9 can then go on to activate caspase 3 and caspase 7, which are responsible for destroying the cell from within. Namid: what are the names for those tests I should be asking for? Will these be accepted by main stream doctors as proof of toxicity and oxidative stress leading to varous symptoms?
|
|
Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Sept 16, 2011 4:01:56 GMT -5
Hi Beebs, I would try nitrotyrosin for nitric stress and caspase 3. I assume with these you should have the best chance that a normal or environmental doctor will do it. I have not much experiences, I just stumbled over that article and I found it interesting. I think we should look, if there are good tests for necrosis because I have the impression that it plays a role directly after taking the quinolone or other big chemicals/drugs. If you find something, let us know. I'll keep my eyes open, too. Best wishes to all of you Namid
|
|
Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Sept 16, 2011 4:12:57 GMT -5
www.antibodybeyond.com/reviews/tumor-markers/necrosis-marker.htmNecrosis (Necrotic) Markers Necrosis (in Greek Νεκρός = Dead) is the name given to accidental death of cells and living tissue. Necrosis is less orderly than apoptosis, which is part of programmed cell death. In contrast with apoptosis, cleanup of cell debris by phagocytes of the immune system is generally more difficult, as the disorderly death generally does not send cell signals which tell nearby phagocytes to engulf the dying cell. This lack of signaling makes it harder for the immune system to locate and recycle dead cells which have died through necrosis than if the cell had undergone apoptosis. The release of intracellular content after cellular membrane damage is the cause of inflammation in necrosis. Morphological Markers - always pathological - involves sheets of cells - energy independent - cell swelling and mitochondrial damage leading to rapid depletion of energy levels - a breakdown of homeostatic control - cell membrane integrity lost - nuclei lost, no DNA cleavage. - cell release of the intracellular contents, leading to an inflammatory response. - dead cells ingested by neutrophils and macrophages After this part several markers are mentioned. We shall take a closer look at them and write down, what may be useful for us.
|
|
|
Post by beebs on Sept 18, 2011 10:16:48 GMT -5
Namid: Thanks for that info. There is little doubt that there is cell death on some level, from severe ADRs, leading to biological premature aging linking the associative (biological) aging process with cytochrome c pathways dysfunction etc.. leading to higher production of caspase-3 Would like to add that some research show its possible to regenerate cells regardless of the trigger, programmed (as in agin, slowing process) or not For eg, research shows that there is cell regeneration in the cardiac myocyte cells following heart attacks. What is the mechanism? We don't know. (see PubMed for ref about this). www.heart-problems.net/myocarditis/Scientists_first_discovered_the_regeneration_of_myocardial_cells_120.htmlSame for nerve cell As for speeding regeneration? Gentle slow detox, Diet (recurrent in scientific reserach), compounds from herbs breathing, meditation, Gi Gong etc... Resveratrol in one study show function in regeneration of cardiac myocyte cells. (see PubMed artciles). As a side note, Resveratrol has been used for thousands of years for heart by Ayurvedic practitioners... PS. Have not found a lab who knew about those tests: nitrotyrosin for nitric stress and caspase 3 I suspect, its not main stream and probably in research centers. We can assume that this is the case, judging by our symptoms, and thus can focus on applying appropriate reversal of damage?? Here is another interesting article: In our case, there is accelerated aging, hence all those symptoms and illness, see the article below which I think is relevant to many of us: Cont/... Because many of the phenotypes of the D257A mice may be explained by loss of specific cell types in the affected tissues, we examined the extent of programmed cell death in this model ( 10). In cells committed to apoptosis, caspase-3 is activated by proteolytic cleavage. Comparison of heart, liver, muscle, and testes from young and old WT mice revealed increases in the amount of cleaved caspase-3 in all of the old tissues examined, indicating that activation of apoptosis is a normal component of aging. D257A mice showed a premature activation of apoptosis in many tissues, including liver, intestine, thymus, testes, and muscle. Elevated amounts of cleaved caspase-3 were present as early as 3 months of age in all of these tissues, except for skeletal muscle, which is postmitotic and where increases were observed after 9 months. Detection of DNA fragmentation during apoptosis via the terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling assay confirmed the increase in apoptosis in thymus, testes, and intestine of 3-month-old D257A mice. These data indicate that the mitochondrial mutator mice bear the hallmarks of accelerated aging, at least in the context of apoptotic cell death. Importantly, in most of these tissues, apoptosis is occurring before the onset of histologic pathology, consistent with a key role for cell death in the phenotypes of the D257A mice. cancerres.aacrjournals.org/content/66/15/7386.full
|
|
Deleted
Deleted Member
Posts: 0
|
Post by Deleted on Sept 20, 2011 23:17:27 GMT -5
|
|
|
Post by beebs on Sept 21, 2011 16:27:25 GMT -5
Thanks Namid, will check this out.
|
|