CURRENT WORK

1 – Does my diet matter for my brain cells?

We are measuring the rate at which dietary polyphenols and their break-down products (said metabolites) get in and out the rat brain. We have discovered that some dietary molecules can enter into the brain, so passing the quite selective blood-brain barrier. Thus, our brain is exposed to some plant- or microbe-derived molecules, which are different from any other compound produced by our cells.

Do my brain cells sense the presence of foreign, dietary molecules?  

We are  checking their biological effects on neuronal & glial cell models.

Why does it matter?

The scientific literature tells that some metabolites of plant polyphenols, which are formed in the gut (the colon) by colonic microbes and then pass into the blood, help neurons remaining active and connected to their neighboring cells. Thus, a healthy intestine may play a role in keeping a healthy brain. The World Health Organization has just warned to do one’s best to protect babies from chronic diarrhea, because they risk an impaired brain development, and may incur in cognitive and behavioral problems.

Can we help people in taking care of their diet?

Every single piece of scientific evidence about the diet-brain interaction (detection, bioactivity) is useful to prepare a frame of dietary recommendations. People want to know more and more about what they eat. Thus, we transfer them the new knowledge, which will enable them to follow the diet-health issue, and build their own empowerment.

The working team

We are sharing these efforts with the team lead by Dr. Fulvio Mattivi, head of the Department of Food Quality and Nutrition in the Research and Innovation Center of Fondazione Edmund Mach (Italy).

Our papers on this topic

  • Gasperotti M, Passamonti S, Tramer F, Masuero D, Guella G, Mattivi F, Vrhovsek U. Fate of microbial metabolites of dietary polyphenols in rats: is the brain their target destination? ACS Chem Neurosci. 2015 Aug 19;6(8):1341-52. doi: 10.1021/acschemneuro.5b00051. Epub 2015 May 5. PubMed PMID: 25891864.
  • Vanzo A, Cecotti R, Vrhovsek U, Torres AM, Mattivi F, Passamonti S. The fate of trans-caftaric acid administered into the rat stomach. J Agric Food Chem. 2007 Feb 21;55(4):1604-11. PubMed PMID: 17300159.
  • Passamonti S, Vrhovsek U, Vanzo A, Mattivi F. Fast access of some grape pigments to the brain. J Agric Food Chem. 2005 Sep 7;53(18):7029-34. PubMed PMID: 16131107.

 

2 – The dream of measuring free bilirubin in biological fluids

We are developing analytical methods to measure free bilirubin in biological fluids and samples. Free bilirubin is the fraction that is not bound to carrier proteins (the main one in serum is albumin). Free bilirubin is the the molecule that can be transported from the cells to the blood and from the blood to the liver.

Bilirubin an a powerful antioxidant, protecting cells from oxidative stress. It is formed in our cells. The main source is the spleen, where damaged red blood cells are trapped and destroyed. So, the broken cells release the heme group of hemoglobin, which is converted to bilirubin by a short sequence of enzymatic reactions. Bilirubin is taken up by the liver, chemically modified and then eliminated into the bile. This process costs energy. The pay off is antioxidant activity and protection of our organs.

Subjects having slightly higher levels of bilirubin in serum, have a lower risk of some chronic diseases (e.g. cardiovascular) that are aggravated by oxidative stress. Thus, bilirubin deserves a special study!

The working team

We are sharing these efforts with the team lead by Prof. Mladen Franko at the University of Nova Gorica (Slovenia), Laboratory for Environmental Research. Another great contribution has been given by the team lead by Prof. Paolo Ugo, Università Ca’ Foscari Venezia (Italy), Department of Molecular Sciences and Nanosystems.

Our papers on this topic

  • Martelanc M, Žiberna L, Passamonti S, Franko M. Direct determination of free bilirubin in serum at sub-nanomolar levels. Anal Chim Acta. 2014 Jan 27;809:174-82. doi: 10.1016/j.aca.2013.11.041. Epub 2013 Dec 1. PubMed PMID: 24418149.
  • Silvestrini M, Mardegan A, Kamath R, Madou M, Moretto LM, Passamonti S, Scopeci P, Ugo P. Pyrolyzed Photoresist Carbon Electrodes in Aprotic Solvent: Bilirubin Electrochemistry and Interaction with Electrogenerated Superoxide. Electrochimica Acta, Volume 147, 20 November 2014, Pages 401-407
  • Passamonti S, Terdoslavich M, Margon A, Cocolo A, Medic N, Micali F, Decorti G, Franko M. Uptake of bilirubin into HepG2 cells assayed by thermal lens spectroscopy. Function of bilitranslocase. FEBS J. 2005 Nov;272(21):5522-35. PubMed PMID: 16262692.

 

2 – The steep march towards describing the structure of bilitranslocase, the bilirubin transporter

The membrane carrier that transports bilirubin into and out of the cells is not properly known. We have an idea, based on many evidences (see below), that the carrier is a polypeptide known as bilitranslocase, classified as TC #2.A.65.1.1.

From this polypeptide, a possible structure has recently been proposed by the group of chemometrics lead by Marjana Novic at the National Institute of Chemistry in Ljubljana (Slovenia). A great work to calculate the 3D structure of bilitranslocase transmembrane domains!

The most recent paper on this topic 

Roy Choudhury A, Sikorska E, van den Boom J, Bayer P, Popenda Ł, Szutkowski K, Jurga S, Bonomi M, Sali A, Zhukov I, Passamonti S, Novič M. Structural Model of the Bilitranslocase Transmembrane Domain Supported by NMR and FRET Data. PLoS One. 2015 Aug 20;10(8):e0135455. doi: 10.1371/journal.pone.0135455. eCollection 2015. PubMed PMID: 26291722; PubMed Central PMCID: PMC4546402.

Previous papers on this topic by Marjana Novic’s group are in PubMed.