Mitogen activated protein kinase kinase Puns

The nucleus says to them "you guys have come a long way from that axon terminal, how'd you find your way here?" Protein kinase A says "well, it would have been tough, but luckily I brought a MAP."

^^I'm ^^sorry.

Title: The Role of Mitogen-Activated Protein Kinase Pathways in Alzheimer’s Disease

Authors: Zhu X, Lee H-G, Raina AK, Perry G, Smith MA

Link: http://www.karger.com/Article/FullText/67426

Thank you in advance!

https://www.ncbi.nlm.nih.gov/pubmed/32211535 ; https://www.sciencedirect.com/science/article/pii/S2405654519301970?via%3Dihub

Xiao H1,2, Zha C1, Shao F3, Wang L1, Tan B2,4.

Abstract

As major fuels for the small intestinal mucosa, dietary amino acids (AA) are catabolized in the mitochondria and serve as sources of energy production. The present study was conducted to investigate AA metabolism that supply cell energy and the underlying signaling pathways in porcine enterocytes. Intestinal porcine epithelial cells (IPEC-J2) were treated with different concentrations of AA, inhibitor, or agonist of mammalian target of rapamycin complex 1 (mTORC1) and adenosine monophosphate activated protein kinase (AMPK), and mitochondrial respiration was monitored. The results showed that AA treatments resulted in enhanced mitochondrial respiration, increased intracellular content of pyruvic acid and lactic acid, and increased hormone-sensitive lipase mRNA expression. Meanwhile, decreased citrate synthase, isocitrate dehydrogenase alpha, and carnitine palmitoyltransferase 1 mRNA expression were also observed. We found that AA treatments increased the protein levels of phosphorylated mammalian target of rapamycin (p-mTOR), phosphorylated-p70 ribosomal protein S6 kinase, and phosphorylated-4E-binding protein 1. What is more, the protein levels of phosphorylated AMPK α (p-AMPKα) and nicotinamide adenine dinucleotide (NAD)-dependent protein deacetylase sirtuin-1 (SIRT1) were decreased by AA treatments in a time depending manner. Mitochondrial bioenergetics and the production of tricarboxylic acid cycle intermediates were decreased upon inhibition of mTORC1 or AMPK. Moreover, AMPK activation could up-regulate the mRNA expressions of inhibitor of nuclear factor kappa-B kinase subunit beta (Ikbkβ), integrin-linked p

http://www.ncbi.nlm.nih.gov/pubmed/26408964

Colorectal cancer is the second deadly cancer in the world. Trametes versicolor is a traditional Chinese medicinal mushroom with a long history of being used to regulate immunity and prevent cancer. Trametes versicolor mushroom extract demonstrates strongly cell growth inhibitory activity on human colorectal tumor cells.

In this study, we characterized a novel 12-kDa protein that named musarin, which was purified from Trametes versicolor mushroom extract and showed significant growth inhibition on multiple human colorectal cancer cell lines in vitro. The protein sequence of musarin was determined through enzyme digestion and MS/MS analysis.

Furthermore, Musarin, in particular, strongly inhibits aggressive human colorectal cancer stem cell-like CD24+CD44+ HT29 proliferation in vitro and in a NOD/SCID murine xenograft model. Through whole transcription profile and gene enrichment analysis of musarin-treated CSCs-like cells, major signaling pathways and network modulated by musarin have been enriched, including the bioprocess of the Epithelial-Mesenchymal Transition, the EGFR-Ras signaling pathway and enzyme inhibitor activity.

Musarin demonstrated tyrosine kinase inhibitory activity in vitro. Musarin strongly attenuated EGFR expression and down-regulated phosphorylation level, thereby slowing cancer cells proliferation. In addition, oral ingestion of musarin significantly inhibited CD24+CD44+ HT29 generated tumor development in SCID/NOD mice with less side effects in microgram doses.

Targeting self-renewal aggressive stem-cell like cancer cell proliferation, with higher water solubility and lower cytotoxicity, musarin has shown strong potence to be developed as a promising novel therapeutic drug candidate against colorectal cancers, especially those that acquire chemo-resistance.

Full text :

- https://www.sciencedirect.com/science/article/pii/S0753332221011239

Full name 5' adenosine monophosphate-activated protein kinase is an enzyme that popped up a lot when I was looking into acetic acid (e.g. [1], [2]). I'm not going to pretend that I know how to analyse this stuff, I'm not a biochemist or even have proper training in medicine, but what I do know for sure is that this enzyme appears a lot when catabolism is involved, and not just for acetic acid.

For example:

Glucagon Activates the AMP-Activated Protein Kinase/Acetyl-CoA Carboxylase Pathway in Adipocytes: http://www.fasebj.org/cgi/content/meeting_abstract/24/1_MeetingAbstracts/995.4

AMPK is the target of Metformin, the most popular anti-diabetic drug: http://circres.ahajournals.org/content/100/3/328.short

Leptin stimulates fatty-acid oxidation by activating AMPK: http://www.nature.com/nature/journal/v415/n6869/abs/415339a.html

Insulin directly affects AMPK in fat: http://www.biovision.com/signaling-pathways-1864/ampk-insulin-and-leptin-signaling-1874

That last implication should ring a lot of bells in our community. Basically all the famous hormones we're talking about are involved in the stimulation or inhibition of AMPK.

PS! Consider this as a "wow, look what I found" note and not a proper biochemistry post. Feel free to make new proper ketoscience posts on it.

User /u/callesen58 was very helpful in a subthread of the vinegar post and he theorized that it may be the acidity itself that does the work and not the type of acid, even though there is evidence that at least in digestion in isolation, that might not be true.

Most generic literature on the enzyme appears to suggest that it's activated when the AMP:ATP ratio changes. I do not know if that's the only way or one of the ways. It appears to make perfect sense when it's done naturally via exercise/hard work, ATP is simply used up.

What is also certain though is that the enzyme appears to be very involved in overall body catabolism when it's activated. And while it is possible that might not be true in all parts of the body, it is almost certain that remedies like stimulati