Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells
Chlamydia pneumoniae directly interferes with HIF-1alpha stabilization in human host cells.
Rupp J, et al
Institute of Medical Microbiology and Hygiene, Center for Structural and Cell Biology in Medicine, University of Luebeck, 23538 Luebeck, Germany.
Chlamydiaceae are obligate intracellulari bacteria that cause endemic trachoma, sexually transmitted diseases and respiratory infections. The course of the diseases is determined by local inflammatory immune responses and the propensity of the pathogen to replicate within infected host cells. Both features require energy which is inseparably coupled to oxygen availability in the microenvironment. Hypoxia-inducible factor-1 (HIF-1) regulates crucial genesi involved in the adaptation to low oxygen concentrations, cell metabolism and the innate immune response. Here we report that Chlamydia pneumoniae directly interferes with host cell HIF-1alpha regulation in a biphasic manner. In hypoxia, C. pneumoniae infection had an additive effect on HIF-1alpha stabilization resulting in enhanced glucose uptake during the early phase of infection. During the late phase of intracellulari chlamydial replication, host cell adaptation to hypoxia was actively silenced by pathogen-induced HIF-1alpha degradation. HIF-1alpha was targeted by the chlamydial protease-like activity factor, which was secreted into the cytoplasm of infected cells. Direct interference with HIF-1alpha stabilization was essential for efficient C. pneumoniae replication in hypoxia and highlights a novel strategy of adaptive pathogen-host interaction in chlamydial diseases.
PMID: 17490410 [PubMed - as supplied by publisher
This cool paper Jim found shows how clever the Cpni really is, it is changing the cell's genes as it lives there so that it can have a favorable environment. Essentially the CPn has taken over the cell's energy and oxygen for its own use, this causes a low oxygen environment. No problem, CPn just changes the cell's genes so the cell can adjust to a low O2 environment by upregulating the HIF-1a. Later in the replication cycle the HIF1a was broken down by injecting protease directly into the cytoplasm of the cell. The upshot is the CPn directly interferes with this adaptive response for its own benefit. Is it any wonder we do not feel well?
no link out, The whole paper is expensive, but I included the whole abstract here. marie
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I had to be this clever to survive so well and to be responsible for so much human misery without being found out I suppose. Any idea when it was published?
Michele: Wheldon CAP1st May 2006 IBSi, sinusitis, alopeciai, asthmai, peripheral neuropathy. 26th March 2007 continuous Flagyli at 400mg with 5 day pulses at 1200mg every three weeks. Spokesperson for Ella, RRMSi Cap Started 16 March 2006
Michèle (UK) GFAi: Wheldon CAPi 1st May 2006. Daily Doxyi, Azi MWF, metroi pulse.
An Itinerary in Light and Shadow
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
Yep, looks like the vote system is not functioning. We'll look into it.
CAPi for Chlamydia pneumonia since 11/04. 25yrs CFSi & FMSi- Currently: 150mg INHi, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tinii daily (Continuous protocol)
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral
This might also account for those times when I just lie there and pant for breath. I think it was Jim K who called it an inability to breathe fluidly, which describes it very well.
The episodes are becoming less frequent, and I am learning to recover more quickly (get under the electric blanket, set to "stun" or higher.)
Ron
On CAPi for CFSi starting 01/06 (NE Ohio, USA)
Currently: doxyi & zithi -- continous; metronidazole -- 5 days on, 7 days off.
Get the research results you paid for: support
Ron
On CAPi for CFSi starting 01/06 (NE Ohio, USA)
Began rifampin trial 1/14/09
Currently: on intermittent
This explains a lot. The hypoxia inside cells would greatly encourage henchmen microbes. High oxygen levels encourage good bacteria. Hypoxia favor pathogens.
Breathing 100% oxygen at ordinary air pressure won't get the oxygen into the cells. Those little oxygen testers placed on a fingertip may say that the blood is well oxygenated, but the patient still be hypoxic. My theory is that without sufficient oxygen, the cell energy machinery can't run, and so hemoglobin synthesis breaks down. Perhaps this is why we get porphyriai.
During weeks of daily hyperbaric oxygen treatments I had no reaction to full doses of all the antibioitics. I think the sufficient level of oxygen inside the cells prevented porphyria and mopped up the endotoxinsi. Insurance currently won't pay for us to get hyperbaric oxygen. Sick, disabled people can't come up with the cash to pay for enough to get them well. Maybe this research into HIF-1alpha could change this.
Or if we just had a pill that would stop the enzyme damage. Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgiai, interstitial cystitisi, sinus: minocycline, Zithromycin, Flagyli
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
Feeling 98% well-going for 100. Very low test for Cpni. CAPi since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NACi,BHRT, MethyB12 FIRi Sauna. 1-18-11 begin new treatment plan with naturopath
As I understand it, porphyriai is caused by inadequate ATP, not inadequate O2. Perhaps someone who knows little more cell biology than I might help us understand the relationship, if any, between intracellulari hypoxia and hemei production. Eric, you around?
CAPi for Chlamydia pneumonia since 11/04. 25yrs CFSi & FMSi- Currently: 150mg INHi, 200 Doxycycline, 500mg MWF Azithromycin, 500mg Tinii daily (Continuous protocol)
CAPi for Cpni 11/04. Dxi: 25+yrs CFSi & FMSi. Currently: 250 aithromycin mwf, doxycycline 100mg BIDi, restarted Tinii pulses; Vit D2000 units, T4 & T3, 6mg Iodoral
If I understand the Krebs cycle, one molecule of glucose is turned into pyruvate, yielding 2 ATP. In the presence of oxygen, the mitochondria then use aerobic respiration to produce 34 molecules of ATP.
Without oxygen the pyruvate is fermented to lactic acid, yielding only 2 ATP.
Also, I have read that hypoxia and cancer are linked.
Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgiai, interstitial cystitisi, sinus: minocycline, Zithromycin, Flagyli
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
Feeling 98% well-going for 100. Very low test for Cpni. CAPi since 8-05 for Cpn/Mycoplasma P.,Lyme, Bartonella, Mold exposure,NACi,BHRT, MethyB12 FIRi Sauna. 1-18-11 begin new treatment plan with naturopath
The HIF-1 alpha research may show the mechanism for what happens in CFSi. This seems to tie together much of what I have read over the years. Mitochondrial failure has been blamed for causing CFS. ADP doesn't get recycled back to ATP fast enough. If someone with CFS thinks they are having a good day, and push too far, ADP may be further broken down to AMP. This causes post exertion fatigue. The body has to start from scratch making ATP.
Some of the supplementsi our good doctors have us taking help this energy cycle. D-ribose. Co enzyme Q. B3 or niacini. Magnesium.
This makes me angrier at cpni. No wonder we feel horrible.
Combined Antibiotic Protocol for chlamydia pneumoniae in fibromyalgiai, interstitial cystitisi, sinus: minocycline, Zithromycin, Flagyli
minocycline, azithromycine, metronidazole 2007-2009, chelation for lead poisoning, muscle pain, insomnia, interstitial cystitisi (almost well), sinus, dry eyes, stiff neck, veins, hypothyroid, TMJ, hip joints (no longer hurt)
Janice, you said, "Also, I have read that hypoxia and cancer are linked." That also might explain why people with CFSi die much younger from cancer if they get it (almost 10 years.)
They get cancer at about the same rate as non-CFS, but die younger.
Ron
On CAPi for CFS starting 01/06 (NE Ohio, USA)
Currently: doxyi & zithi -- continous; metronidazole -- 5 days on, 7 days off.
Ron
On CAPi for CFSi starting 01/06 (NE Ohio, USA)
Began rifampin trial 1/14/09
Currently: on intermittent
Janice
I have problems with altitudes too
How are you doing in that respect now?
DAILY: NACi 2400MG , DHEAi sublingual , CoQ10 200 mg, vit D3 2,000 IU, multi vits, Folapro, Doxyi 200 mg. 2 or 3 PER WEEK Astaxanthin, Azithromycin 250 mg,B12, Coffee retension enema, Flagyli 6 day pulse, Thyme Thujanol twice a week
For anyone interested, the full paper "Chlamydia pneumoniae directly interferes with HIF-1α stabilization in human host cells" can be read here:
http://onlinelibrary.wiley.com/doi/10.1111/j.1462-5822.2007.00948.x/full
Janice
You said
If someone with CFSi thinks they are having a good day, and push too far, ADP may be further broken down to AMP. This causes post exertion fatigue. The body has to start from scratch making ATP.
That makes the most sense so far
DAILY: NACi 2400MG , DHEAi sublingual , CoQ10 200 mg, vit D3 2,000 IU, multi vits, Folapro, Doxyi 200 mg. 2 or 3 PER WEEK Astaxanthin, Azithromycin 250 mg,B12, Coffee retension enema, Flagyli 6 day pulse, Thyme Thujanol twice a week