UVB, PGE2/PGD2 and astaxanthin

UVB light upregulates prostaglandin synthases and prostaglandin receptors in mouse keratinocytes
Black, Adrienne T. | Gray, Joshua P. | Shakarjian, Michael P. | Mishin, Vladimir | Laskin, Debra L. | Heck, Diane E. | Laskin, Jeffrey D.
Toxicology and applied pharmacology  2008;232(1):14-24.

http://www.ncbi.nlm.nih.gov/pubmed/18597804

Prostaglandins belong to a class of cyclic lipid-derived mediators synthesized from arachidonic acid via COX-1, COX-2 and various prostaglandin synthases. Members of this family include prostaglandins such as PGE2, PGF2α, PGD2 and PGI2 (prostacyclin) as well as thromboxane. In the present studies we analyzed the effects of UVB on prostaglandin production and prostaglandin synthase expression in primary cultures of undifferentiated and calcium-differentiated mouse keratinocytes. Both cell types were found to constitutively synthesize PGE2, PGD2 and the PGD2 metabolite PGJ2. Twenty-four hr after treatment with UVB (25 mJ/cm2), production of PGE2 and PGJ2 increased, while PGD2 production decreased. This was associated with increased expression of COX-2 mRNA and protein. UVB (2.5 – 25 mJ/cm2) also caused marked increases in mRNA expression for the prostanoid synthases PGDS, mPGES-1, mPGES-2, PGFS and PGIS, as well as expression of receptors for PGE2 (EP1 and EP2), PGD2 (DP and CRTH2) and prostacyclin (IP). UVB was more effective in inducing COX-2 and DP in differentiated cells and EP1 and IP in undifferentiated cells. UVB readily activated keratinocyte PI-3-kinase (PI3K)/Akt, JNK and p38 MAP signaling pathways which are known to regulate COX-2 expression. While inhibition of PI3K suppressed UVB-induced mPGES-1 and CRTH2 expression, JNK inhibition suppressed mPGES-1, PGIS, EP2 and CRTH2, and p38 kinase inhibition only suppressed EP1 and EP2. These data indicate that UVB modulates expression of prostaglandin synthases and receptors by distinct mechanisms. Moreover, both the capacity of keratinocytes to generate prostaglandins and their ability to respond to these lipid mediators are stimulated by exposure to UVB.

Astaxanthin attenuates the UVB-induced secretion of prostaglandin E2 and interleukin-8 in human keratinocytes by interrupting MSK1 phosphorylation in a ROS depletion–independent manner
Terazawa S, Nakajima H, Shingo M, Niwano T, Imokawa G.
School of Bioscience and Biotechnology, Tokyo University of Technology, Hachioji, Tokyo, Japan. kimura@nagahp.jp

http://www.ncbi.nlm.nih.gov/pubmed/22626465

To elucidate the effects of redox balance regulation on cutaneous inflammation, we used the potent antioxidant astaxanthin (AX) to assess its effect on the UVB-induced secretion of PGE2 and IL-8 in human keratinocytes and analysed its biological mechanism of action. The addition of AX (at 8 μm) to human keratinocytes even after UVB irradiation significantly down-regulated the increased secretion of PGE2 or IL-8. Those suppressive effects were accompanied by significantly decreased expression of genes encoding COX-2 or IL-8 as well as COX-2 protein. Analysis using a specific NF-κB tanslocation inhibitor demonstrated that the UVB-stimulated secretion of PGE2 and IL-8 was significantly abolished by its treatment prior to UVB irradiation. Western blotting of phosphorylated signalling molecules revealed that UVB irradiation (80 mJ/cm2) significantly stimulated the phosphorylation of p38, ERK and JNK, which was not suppressed by treatment with AX after irradiation. In contrast, AX significantly inhibited the UVB-increased phosphorylation of mitogen- and stress-activated protein kinase (MSK)-1, NF-kBp65 or CREB even when treated postirradiation. Further, the MSK1 inhibitor H89 significantly down-regulated the increased secretion of PGE2 and IL-8 in UVB-exposed human keratinocytes, following post-irradiation treatment. These findings suggests that AX attenuates the auto-phosphorylation of MSK1 required for its activation, which results in the decreased phosphorylation of NF-kBp65, which in turn probably leads to a deficiency of NF-kB DNA binding activity. This may be associated with the significant suppression of PGE2/IL-8 secretion via the down-regulated expression of COX-2 and IL-8 at the gene and/or protein levels.

So, assuming sunlight raises PGE2 disproportionately to PGD2, or even reduces the production PGD2 as it did with mouse study, then it would seem to me that supplementing with astaxanthin, despite its benefits, would be unwise prior to sun exposure if raising PGE2 was one's goal.

My question is, how long would one have to drop the astaxanthin prior to sun exposure?  Because in my limited internet searching I have been unable to find what the exact half-life is, given the fact it can accumulate in the body over time.

I believe PGD2 is the real villain here, and this goes to show that sunlight should help attenuate it. If anything (I will have to try to dig up something on this) I believe PGE2 is the more beneficial type of prostaglandin, and the pathway we'd rather the process go.

I have always suspected sunlight exposure to my scalp had something to do with things, but I was always sure it had to do with vitamin D. This is very important evidence. I have never seen my hair thin out faster and my scalp be more inflamed than when I went through my hat phase. My scalp got almost no sun exposure for a very, very long time, and during that time my hair virtually disappeared. I thought I was doing my scalp a favor but I wasn't.

Something about sun exposure on the skin is an extremely primal exposure and I have to imagine it effects our physiology hugely. During the great majority of our adaptive history we were exposed to huge amounts of sunlight compared with what we get today. Is that effecting rates of hairloss? I wouldn't be surprised.

So Astaxanthin would be working against us when trying to get sun exposure?

Prostaglandin D2 Inhibits Hair Growth and Is Elevated in Bald Scalp of Men with Androgenetic Alopecia
Luis A. Garza, Yaping Liu, [...], and George Cotsarelis
Sci Transl Med. 2012 March 21; 4(126): 126ra34.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319975/

PGE2 and PGF2α have been shown to enhance hair growth in mice (20). Our studies show that prostaglandins are dysregulated in AGA, the most common type of hair loss in men. Specifically, PGD2 inhibits hair growth and thus represents a negative counterbalance to the positive effects on hair growth shown for PGE2 and PGF2α.

Our results suggest that in mouse and human skin, a balance between PGE2 and PGD2 controls hair growth. This model predicts then that efforts to reverse alopecia should optimally focus on both enhancing PGE2 and inhibiting PGD2 signaling. This model also explains why agents such as aspirin, which inhibit upstream prostaglandin synthesis enzymes (PTGS1 and PTGS2), have minimal effects on hair growth because of likely equally decreased production of PGE2 and PGD2

evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although minoxidil alters potassium channel kinetics (7), it is also known to increase production of PGE2 (37). Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can concomitantly decrease PGD2 levels and thus normalize multiple prostaglandin species as a mechanism to improve AGA.

theseeker86 wrote:So Astaxanthin would be working against us when trying to get sun exposure?

I'm no scientist but the in vitro study suggests to me it would stop PGE2 production in its tracks. Of course, would always like to hear what CS has to say.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3319975/

"Additional evidence that prostaglandins control hair follicle cycling and can be used therapeutically to treat AGA arises from findings on the possible mechanism of the AGA drug minoxidil. Although minoxidil alters potassium channel kinetics, it is also known to increase production of PGE2. Given the decreased amount of PGE2 present in bald scalp versus haired scalp (Fig. 2E), minoxidil may normalize PGE2 levels. Future studies should address whether minoxidil can concomitantly decrease PGD2 levels and thus normalize multiple prostaglandin species as a mechanism to improve AGA."


If sunlight is able to positively alter these levels in the scalp skin, that is very interesting. Overall, any strategies that are able to promote a better ratio of PGE2:PGD2 should be very beneficial for hair loss. Its worth research. I'd like to examine how the stress hormones effect these metabolites.

A good post, I guess we should all try more sun exposure this summer.

As far as my knowledge of prostaglandins go, I share the sentiment that PGD2 seems to harm the hair. PGE2 seems to help keep hair, but slows down the rate of hair growth. But the speed of hair growth is not what we should be bothered with.

The richest natural food sources of astaxanthin are red or pink fish, seafoods and algae sourced from the sea. This includes krill and shrimp which are rich in astaxanthin. So, for someone who will try to go by the study in OP, these are the foods to reduce consumption of while you are sunbathing.

Sucks it's winter in Aus right now, i really need to get more sun exposure that's for sure.  I'm sure people would say I'm joking when i say how much i actually get and it's not good at all.

I wonder if after adequate sun exposure during the day we could resume with the astaxanthin in the evening?

Sunlight exposure Vitamin D calculator. Basically, it could be called a UVB calculator as well.
http://nadir.nilu.no/~olaeng/fastrt/VitD-ez_quartMED.html

theseeker86 wrote:Sucks it's winter in Aus right now, i really need to get more sun exposure that's for sure.  I'm sure people would say I'm joking when i say how much i actually get and it's not good at all.

I wonder if after adequate sun exposure during the day we could resume with the astaxanthin in the evening?

Refer to table 1 and you will see that even consuming 1 mg of astaxanthin daily will accumulate in the system.  

So, one would need to clear the astaxanthin from their bodies on a regular basis if they were to be able to supplement and then be able to get the desired effects from sunlight soon enough thereafter.

The half-lives reported for astaxanthin range from 15.9+/-5.3 h for a single 40 mg dose of astaxanthin provided to healthy male volunteers (abstract does not say how many participants) to 52+/-40 h in a study where 3 middle-aged volunteers were given a 10 mg dose and weeks later a 100 mg dose of astaxanthin (so therefore a 12 hour half-life for the small dose.)

But since I don't know what amount of astaxanthin in the body would be enough to inhibit PGE2 production, I can't recommend when to stop supplementing.

But FWIW my plan is going to be:  4 mg of astaxanthin on Monday night, and 2 mg Tuesday morning, with krill oil in the morning Tuesday and Wednesday. Then fish oil (with vitamin E to preserve it) the remaining days, and sun exposure Saturday and Sunday.

For me It's counterintuitive that blocking PGE2 with natural substances could hinder the hair regrowth potential.