Fetuin

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Fetuins are blood proteins that are made in the liver and secreted into the blood . They belong to the large group of binding proteins in the blood that are responsible for the transport and availability of substances of various kinds in the bloodstream . The best-known representative of these transport proteins is serum albumin , the most common protein in terms of quantity in the blood serum of adult animals. In contrast, fetuin occurs in particularly large amounts in fetal blood. This is where the name Fetuin (Latin fetus ) comes from . For example, fetal bovine serum contains more fetuin than albumin, whereas adult serum contains much more albumin than fetuin.

X-ray images of a Fetuin-A knockout mouse (- / -) compared to a normal mouse (+ / +), the so-called wild type

Fetuins are members of a family of proteins that evolved from the smaller protein cystatin through gene duplication and the exchange of gene segments . Fetuins thus belong to the so-called cystatin superfamily of proteins, which also include the histidine-rich glycoprotein (HRG) and the kininogens (KNG).

Human α 2 -HS glycoprotein (genetic symbol AHSG) is known synonymously as α 2 -HS, A2HS, AHS, HSGA and Fetuin-A. Fetuin-A is present in one copy in the genome . In 2000 the closely related fetuin-B was discovered in the human, rat and mouse genome. Like Fetuin-A, Fetuin-B is mainly formed by the liver, but also by a number of other secretory organs. Fetuins are found in all vertebrate genomes studied to date, including fish and reptiles.

Representative

Two different fetuins are currently known: Fetuin-A and Fetuin B.

Fetuin-A

The function of fetuin-A in the body was elucidated by gene knockout in mice. Feeding a diet rich in minerals caused calcification of the lungs, heart and kidneys in these mice . The calcification reached dramatic proportions when the fetuin-A knockout was crossed into mice with the genetic background DBA / 2. This mouse strain naturally has a tendency to calcify injured tissue. The fetuin-A deficiency increased the tendency to calcification very dramatically and completely without a mineral-rich diet. Therefore, Fetuin-A is considered to be a potent inhibitor of calcification in the blood. This type of calcification is extremely rare and can best be compared with the clinical picture of calciphylaxis . It is only indirectly related to the commonly known hardening of the arteries, arteriosclerosis .

Fetuin-A is increased in a fatty liver . Fetuin-A inhibits adiponectin and increases the level of tumor necrosis factor alpha (TNFα), which has an inflammatory (pro-inflammatory) effect on the blood vessels. Fetuin-A binds to insulin receptors in muscles and fat cells and contributes to insulin resistance . According to initial studies, people with high fetuin-A values ​​have a 3 to 4-fold increased risk of stroke and heart attack. A study on dialysis patients also showed a significantly increased inflammatory activity, vascular calcification and an increased risk of cardiovascular and non-cardiovascular death in subjects with decreased fetuin A values ​​due to a genetic polymorphism. If a suitable laboratory standard is developed, Fetuin-A may be suitable as an independent marker for cardiovascular risks.

Fetuin-B

Fetuin B plays an important role in the regulation of the zona pellucida ; the protein inhibits ovastacin , which causes the zona pellucida to harden even before a sperm can penetrate. Female mice without Fetuin-B are - despite normal development and function of the ovaries - sterile.

Individual evidence

  1. ^ A b E. Olivier, E. Soury, P. Ruminy, A. Husson, F. Parmentier, M. Daveau, JP Salier: Fetuin-B, a second member of the fetuin family in mammals. In: Biochem J. 2000 Sep 1; 350, pp 589-597. PMID 10947975 .
  2. ↑ Karin Wilbrand: Fetuin A concentration marks cardiovascular risk. Obesity Foundation Germany, January 22, 2009.
  3. ↑ C. Weikert, N. Stefan, MB Schulze et al .: Plasma fetuin-a levels and the risk of myocardial infarction and ischemic stroke . In: Circulation . tape 118 , no. December 24 , 2008, pp. 2555-2562 , doi : 10.1161 / CIRCULATIONAHA.108.814418 , PMID 19029462 .
  4. ↑ Stenvinkel P, Wang K, Qureshi AR, Axelsson J, Pecoits-Filho R, Gao P et al .: Low fetuin-A levels are associated with cardiovascular death: Impact of variations in the gene encoding fetuin. Kidney Int. 2005 Jun; 67 (6): 2383-92. PMID 15882283 doi: 10.1111 / j.1523-1755.2005.00345.x
  5. ↑ Fertility: important mechanism found. Report to DocCheck from April 19, 2013.
  6. ↑ Eileen Dietzel et al: Fetuin-B, a Liver-Derived Plasma Protein Is Essential for Fertilization. In: Developmental Cell. Vol. 25 (1), pp. 106-112, April 4, 2013, doi: 10.1016 / j.devcel.2013.03.001 .

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