Interesting Study on the importance of Leukotriene B4 for differentiation of Neural Stem Cells into Neurons

 

Just doing some googling on leukotrienes and lipoxins and ran across this study.   If the findings are correct, it might also indicate that caution might be warranted in using 5-LOX inhibitors and Leukotriene B4 blockers in CNSi disease:

Leukotriene B4 and lipoxin A4 are regulatory signals for neural stem cell proliferation and differentiation<

Some interesting quotes from the article:

"Here we describe for the first time the potent neuronal regulatory functions of these bioactive LOX products. Activation of the LTB4 signaling pathways in NSC by physiological levels of LTB4 promoted stem cell proliferation. Excessive activation of LTB4 signaling, with higher concentrations of LTB4 (>3 µM), resulted in inhibition of NSC growth. This biphasic action of LTB4 suggests that LTB4 signaling tightly regulates proliferation of NSCs and indicates that optimal amounts in vivo of local LTB4 might play a role in NSC survival and proliferation.

Consistent with this role of LTB4 signaling in regulating NSC proliferation, 5-lipoxygenase inhibitors and LTB4 receptor antagonist caused apoptosis of NSCs. It is of note that proliferation of human neuronal precursor cells was also blocked by 5-lipoxygenase inhibitor (25)< . These results suggest that LTB4 signaling regulates NSC growth and that programmed cell deathi ensues in its absence."

 

"Of particular interest, LTB4 stimulated the differentiation of NSCs into neurons. This was confirmed by increased neurite outgrowth and increased expression of MAP2, as well as by increased expression of several channels and receptors, such as voltage-gated sodium channel, potassium channel, chloride channel, and nicotinic receptor. Increased levels of these molecules are required for the maturation of differentiated neurons. The present results indicate that LTB4 signals not only proliferation, but also differentiation of NSCs into neurons. In general, it is rare to observe markers of both proliferation and differentiation at the same stage in somatic cells. The mechanisms underlying stimulation of differentiation by LTB4 may differ from those required for proliferation. NSCs are considered multipotent cells that have the ability of both "self-renewal" and "differentiation." Therefore, it might be unique to the NSC system to exhibit both proliferation and differentiation phenotypes in response to LTB4.

Visible disorders were not observed for 5-lipoxygenase knockout mice during development, although various different responses against inflammationi and other pathological conditions were observed with 5-lipoxygenase knockout mice compared with those of wild-type (WT) mice (27< 28< 29)< . These reports and our observations in the present study indicate that bioactions of 5-lipoxygenase-derived lipid mediators described in this study may be more relevant in pathophysiological conditions such as PD, Huntington’s disease, nerve injury, stroke, and multiple sclerosis than for normal CNS development and maturation."

 

See more about 5-LOX inhibitors and Leukotriene B4 blockers here:

Cathelicidins and LTB4<

 

 

 

Red, I noticed that green tea was listed as an inhibitor but not black tea. I stopped taking curcumin but have been drinking tea (black and green) with caffiene to counteract the headaches while getting used to the Nitro patch.

Any information about coffee being an inhibitor?

Thanks for the post. You always dig up the most interesting information.

Raven

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

Hi Raven,

I'll have to look up black tea, but I know green tea catechins have been identified as an inhibitor.    CafFeic acid found in coffee has been identified as an inhibitor as well:

Caffeic acid attenuates the decrease of cortical BDNF transcript IV mRNA induced by swim stress in wild-type but not in 5-lipoxygenase-deficient mice<.

Wikipedia:  Caffeic Acid <

I'm not sure how much of the 5-LOX inhibitors are actually found in a cup of green tea or coffee though...

Treatment for Rosaceai<

  • CAPi:  01/06-07/07
  • High-Dose Vit D3, NACi:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Hi Raven,

I could only find a couple of places that suggest that black tea may have 5-lipoxygenase activity:

Pharmacological studies on Indian black tea (leaf variety) in acute and chronic inflammatory conditions.<

US Patent 7108868 - Isolation of a dual cox-2 and 5-lipoxygenase inhibitor from acacia<

Apparently green tea has a higher content of catechins than black tea though...

Again, I doubt seriously if a cup or two of green tea is going to hurt much.      Consumption in very large quantities (via supplementsi, etc) might not be that great of an idea though...

Hope this helps...

 

Treatment for Rosaceai<

  • CAPi:  01/06-07/07
  • High-Dose Vit D3, NACi:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

Red, isn't it ironic that those substances that reduce inflammationi are also standing in the way of fully whacking the infection? Now I am wondering if luteolin is on this list of 5 Lox inhibitors. I ran out of Lutimax a while ago and just reordered it.

Raven

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

Hi Raven,

It is, kind of.   The real problem is that too much, chronic inflammationi is destructive, but inflammation is, however, part of the healing response.   

There's not much in pubmed on luteolin, but there is some research that suggests that it likely has 5-LOX inhibiting qualities:

 

Structure-activity relationship for antiinflammatory effect of luteolin and its derived glycosides<

US Patent 6217875 - Inhibitors of lipoxygenase<

Be sure to run this by your doctor (as you know)...

 

Treatment for Rosaceai<

  • CAPi:  01/06-07/07
  • High-Dose Vit D3, NACi:  07/07-11/08
  • Intermtnt CAP, HDose Vit D3:  11/08-01/09
  • HDose Vit D3, Mg, Zn: 01/09-

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