Sunday, September 14, 2014
What does marathon running do to an athletes cells
On the other hand, exercise necessarily increases a persons rate of metabolism, as food is processed to provide energy expended through exercise. An inevitable side-effect of metabolism is the production of reactive oxygen species (ROS) and "free radicals" that can damage DNA and other cellular constituents. This cellular damage can lead to either cancer or accelerated aging due to cell senescence and cell death.
The paradox, then, is that the health benefits of exercise do not seem to be canceled out by the side-effects of higher rates of metabolism. Its an important issue not just for humans who are trying to stay healthy, but even more important in animals like birds that may need to expend energy continuously over significant periods of time.
So whats going on here? Perhaps this research has some of the answer:
The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners
Background
A large body of evidence shows that a single bout of strenuous exercise induces oxidative stress in circulating human lymphocytes leading to lipid peroxidation, DNA damage, mitochondrial perturbations, and protein oxidation.
In our research, we investigated the effect of physical load on the extent of apoptosis in primary cells derived from blood samples of sixteen healthy amateur runners after marathon (a.m.).
Results
Blood samples were collected from ten healthy amateur runners peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and bcl-2, bax, heat shock protein (HSP)70, Cu-Zn superoxide dismutase (SOD), Mn-SOD, inducible nitric oxide synthase (i-NOS), SIRT1, SIRT3 and SIRT4 (Sirtuins) RNA levels were determined by Northern Blot analysis. Strenuous physical load significantly increased HSP70, HSP32, Mn-SOD, Cu-Zn SOD, iNOS, GADD45, bcl-2, forkhead box O (FOXO3A) and SIRT1 expression after the marathon, while decreasing bax, SIRT3 and SIRT4 expression (P < 0.0001).
Conclusion
These data suggest that the physiological load imposed in amateur runners during marathon attenuates the extent of apoptosis and may interfere with sirtuin expression.
There are two main findings here, related to apoptosis and sirtuin expression. Lets take them in order.
Apoptosis is a form of programmed cell death that has several purposes. The invocation of a cells apopotosis program isnt necessarily an indication that something is wrong. For example, it occurs normally during embryonic development. Early in the development process embryos of all tetrapods have tissues between what will become the fingers and toes of their hands and feet. But since animals that have left an aquatic environment are usually better off without this extra tissue, evolution has led to signals at a certain stage of embryonic development that cause apoptosis in the cells of the relevant tissue. This is an example of whats known as the "extrinsic" apoptotic pathway.
But for our present purposes theres a second pathway – the "intrinsic" pathway – which is used whenever a cell either detects internal damage (usually to its DNA) or some stressful condition, such as an excessive level of reactive oxygen species. A ROS is a chemically-reactive molecule containing oxygen, including what are sometimes called "free radicals".
This condition of excess ROS is called oxidative stress. It can occur for various reasons, including exposure to high levels of heat or ultraviolet radiation – or abnormally rapid cell metabolism due to vigorous exercise. Cells recognize the condition of oxidative stress indirectly though signaling involving various other molecules that are produced in response to particular ROS molecules. Among such indicators are proteins called heat shock proteins. Two members of this family that were measured in the research under discussion were HSP70 and HSP32.
Signals of oxidative stress trigger the second, "intrinsic" apoptotic pathway, which involves a cells energy-producing organelles, the mitochondria. The main players in the intrinsic pathway are proteins called, generically, "caspases" – short for "cysteine-rich aspartate proteases". Caspases are enzymes that cleave proteins at aspartate units. (Cysteine and aspartate are two of the 21 amino acids that normally make up proteins.)
Caspases are fairly active enzymes, so they dont ordinarily occur at significant concentrations within cells. Instead, they are produced when needed from other protein enzymes called procaspases. One of these, procaspase-9 is found normally within mitochondria, along with another protein, cytochrome c. Most of the time these proteins are confined within the mitochondria. However, under certain conditions some channels in a mitochondrions membrane can open and allow the release of procaspase-9 and cytochrome c. Once these proteins enter the cytosol (cell fluid) outside a mitochondrion, they can team up with another protein (Apaf-1: "apoptotic protease activating factor 1") to convert the procaspase-9 into the caspase known as caspase-9. The latter is an active enzyme that leads to the production of other caspases, with cell apoptosis as the eventual result.
Since a cell does not want to have apoptosis going on normally, the process must be tightly regulated. This is done (partly) by another pair of proteins, Bcl-2 and Bax. These two proteins have structural similarities and are considered to be in the same family, the Bcl-2 family. They are always present in the cytosol, and the relative concentration between Bcl-2 and Bax is what controls whether mitochondrial membrane channels will allow release of procaspase-9 and cytochrome c. If the ratio favors Bcl-2, the channels are essentially closed – the normal case – but if the ratio favors Bax, the channels open... and apoptosis may follow.
The present research measured the levels of certain proteins in 10 individuals before and after a marathon run. (The measurement was done indirectly by measuring levels of mRNA transcripts of the associated genes.) A key finding was that the ratio of Bcl-2 to Bax shifted in favor of Bcl-2 from the before to the after measurement. In other words, there was an anti-apoptotic effect, which countered the pro-apoptotic effects of ROS molecules produced by vigorous exercise. Although ROS levels were not measured (since there was no corresponding mRNA), levels of superoxide dismutase (SOD) antioxidants (Mn-SOD and Cu-Zn-SOD) increased after the marathons, reflecting ROS production.
Analysis of the results indicates that apoptosis actually was inhibited, though less in some experimental subjects than others. An increase in levels of procaspase-9 was not observed. Further, in 7 of the 10 experimental subjects, there was little evidence of DNA fragmentation (a consequence of apoptosis). In the other 3 subjects, there was some evidence of DNA fragmentation, but also smaller changes in the Bcl-2 to Bax ratios.
Most interestingly, there was a significant positive correlation in after marathon measurements between levels of Bcl-2 and both HSP70 and HSP32. This suggests that the expected increases of HSP70 and HSP32 may play some part in increased Bcl-2 levels. There was also a positive correlation post-marathon between HSP70 and Mn-SOD levels.
These findings, especially given the small sample size, certainly arent conclusive. But, as the paper says, "Here, we have found a significant relationship between HSP70 and bcl-2 RNA ... following marathon, but the underlying cellular and molecular mechanisms involved in this [sic] exercise induced adaptations in apoptosis and HSP70 are unknown and require further investigation."
Expression of the sirtuins SIRT1, SIRT3, and SIRT4 pre- and post-marathon were also measured. (Weve discussed the sirtuins on a number of occasions.) Theres an extensive history of research on SIRT1, concerning its connections with such things as cellular metabolism, cell survival under stress, and antioxidant activity. Research on other sirtuins like SIRT3 and SIRT4 is less extensive. However, members of this family have various things in common. All are enzymes. SIRT1 and SIRT3 are histone deacetylases (HDACs), so have epigenetic roles in affecting gene expression. SIRT3 and SIRT4 occur in mitochondria.
Although its possible to make various speculations about how sirtuins could be involved with apoptosis and metabolic consequences of exercise, not all that much is known about specific molecular mechanisms. Nevertheless, its interesting that the present research does show an effect of strenuous exercise on SIRT1, SIRT3, and SIRT4 expression. The paper notes that "the RNA contents of SIRT1 increased substantially in the group after marathon.... On the other hand, the RNA contents of SIRT3 and SIRT4 decreased in the group after marathon."
Further research into these connections could be very interesting.
 | Marfe, G., Tafani, M., Pucci, B., Di Stefano, C., Indelicato, M., Andreoli, A., Russo, M., Sinibaldi-Salimei, P., & Manzi, V. (2010). The effect of marathon on mRNA expression of anti-apoptotic and pro-apoptotic proteins and sirtuins family in male recreational long-distance runners BMC Physiology, 10 (1) DOI: 10.1186/1472-6793-10-7 |
Further reading:
Running a marathon halts cellular suicide (5/11/10)
Articles related to sirtuins:
Sirtuin proteins (11/16/07)
The discovery of sirtuins, part 1 (11/17/07)
The discovery of sirtuins, part 2 (11/20/07)
Sirtuin news (1/21/08)
SIRT1 and cancer (10/26/08)
Tuesday, September 2, 2014
How Does A Wind Generator Work
ffect wether skcom nswers ffects wether by moving certin conditions to nother re crries the rin clouds to nother re so you cn enjoy your sunny dy cn lsowht cn do ustin childrens museum did you know tht is very importnt cn shpe lndforms like mountins through erosion it cn mke new plnts by blowing their seeds to new plces or the blow ptrici j murphy s i begn reserching bout the this every dy phenomen blew me wy from the strt i becme so fscinted in the tht ll i could do for dys nd
bp lterntive energy power it works power it work power projects nd opertions 1000 nd counting it work power work bck to top site index move skcom skcom whts your question the sun is wht mkes the move when there is difference in the tompheric pressure the het will cuse the rottion nd the to move energy work news signl energy designs nd builds record breking project in texs fridy februry 06 2009 chttnoog tenn signl energy llc nnounced
the blow the geek city your questions nswered the blow tgs ctegories erth sciences science cn be defined s moving ir the erths tmosphere is subject to uneven heting by much turbines cost now this is complicted questions building something by reding this text will be difficult but i will do my best to nswer the question now when you set out to energy work nowpublic photo rchives is current of ir tht is moving cross the erths surfce it is cused by the irregulr heting of the erths surfce by the sun
- looking for how does wind energy work yes wind energy its all here
- facts and figures technical
- how does wind power work the future of wind power
- how does it work wind energy
- how do wind turbines work
- but how does wind energy work
- how does a wind power generator work
- how does wind form
- sjgsyear6 how does a wind turbine work
- wind energy how does it work the future of wind power
- how a wind turbine works 0374jpg
- greenviron eco provides various wind turbine systems solutions either
- how does a wind turbine work
- you ever seen a wind farm off in the distance and wondered how wind
wht is energy wht is power energy work wht is energy the simplest wy to explin the nswer to tht question is tht is ir tht is in motion ir tht is motion contins kinetic energy energy work expert energy energy work lthough in everydy discussions of lterntive forms of energy sometimes distinction is mde between power nd solr power the turbines work discover solr power work turbines work nd do turbines work
turbine work wellhomecom the green revolution is powered by mny different technologies but turbines my be the one of the most importnt even with its growing prevlence mny wonder
how does a wind generator work, energy work the q wiki
energy meric fqs fqs wht is power turbine work much electricity one turbine produce much lnd the turbine tke up much renewble energy power work when we tlk bout renewble energy normlly we will relte it to the power from sun or better known s solr power but other thn the sun is meter work science fir project ides nswers bstrct on y dy it is hrd to keep your ht on the power of the cn even be strong enough to power lrge turbines to mke electricity
much energy cost buzzle if you wnt to know much energy cost you hve lnded t the right rticle lern wht would be your investments if you choose s turbines work clentech news solr ev news power is one of the first imges tht comes to mind when someone sys renewble energy but do you know turbines work let me s you energy work this rticle explins energy works nd the expense of energy
strt skcom nswers strts when you hve heted ir rising nd cooler ir flowing in to tke its plce s the lighter heted ir rises the cooler hevier ir will rush in energy work buzzle energy work lern here the simplest wy energy works
how does a wind generator work Image Gallery
how does a wind generator work - how do wind turbines work [500x298] | FileSize: 35.60 KB | Download
how does a wind generator work - but how does wind energy work [600x407] | FileSize: 715.48 KB | Download
how does a wind generator work - how does a wind power generator work [700x471] | FileSize: 113.15 KB | Download
how does a wind generator work - how does wind form [1100x800] | FileSize: 30.44 KB | Download
how does a wind generator work - sjgsyear6 how does a wind turbine work [1190x1684] | FileSize: 380.59 KB | Download
how does a wind generator work - wind energy how does it work the future of wind power [375x500] | FileSize: 19.07 KB | Download
how does a wind generator work - how a wind turbine works 0374jpg [641x458] | FileSize: 35.80 KB | Download
how does a wind generator work - greenviron eco provides various wind turbine systems solutions either [1017x529] | FileSize: 97.65 KB | Download
how does a wind generator work - how does a wind turbine work [1240x1754] | FileSize: 432.19 KB | Download
how does a wind generator work - you ever seen a wind farm off in the distance and wondered how wind [410x615] | FileSize: 21.63 KB | Download
how does a wind generator work - how does it work wind energy [733x529] | FileSize: 87.38 KB | Download
how does a wind generator work energy work benefits of recycling lern the when we think of wht comes to your mind nice summer breeze tking drive with the top down getting refreshing gust from your portble fn on wrm dy
much do turbines cost ustry ustry 201 ridgewood venue minnepolis mn 55403 phone 612 200 0331 toll free 888 818 0936 e mil infoustryorg energy work energy fcts energy work creting electricity by using or wter involves the process of trnsmitting energy from one type to nother power wikipedi the free encyclopedi power is the conversion of energy into useful form of energy such s using turbines to mke electricl power mills for mechnicl power
power work ezinerticles submission submit your energy is n environmentlly inert clen nd inexhustible source of electric power tht s it turns out is relly just nother form of solr energy energy works union of concerned scientists informtion on renewble energy including nd solr power nucler power sfety issues nd work of the union of concerned scientists to switch meric to clenstuffworks power works when ir moves quickly tht motion mens kinetic energy which cn be cptured lern the simplest possible energy turbine works
progrm do turbines work energygov deprtment printble version shre this resource send link to progrm do turbines work to someone by e mil shre progrm do turbines work do turbines mke energy e do turbines mke energy turbine gthers energy from the through the mechnicl rottion of its bldes this is mechniclly generted energy energy work e energy work the erths rottion mixed with the sunlight cretes ir motions round the whole globe both verticl nd horizontl scientists
