INVESTIGATION OF THE N-TERMINAL CODING REGION OF MUC7 ALTERATIONS IN DENTISTRY STUDENTS WITH AND WITHOUT CARIES
Koç Öztürk L, Yarat A, Akyuz S, Furuncuoglu H, Ulucan K,
*Corresponding Author: Dr. Korkut Ulucan, Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Üsküdar University, Haluk Turksoy Sok. No. 14, Üsküdar, İstanbul 34662, Turkey. Tel: +90-216-400-2222-2409. Fax: +90-216-400-2222; Mobile: +90-532-692-1922. E-Mail: korkutulucan@hotmail.com
page: 71

DISCUSSION

Mucins coat the gastrointestinal, genito-urinal and respiratory tracts, as well as the oral cavity. In the oral cavity, they have a variety of functions such as lubricating and protecting the oral cavity and providing a nonspecific immune defense [10]. In our cohort, OHI-S, GI, salivary pH, flow rate, buffering capacity and total protein levels were not significantly different between the two groups. These parameters have important effects on oral hygiene, and also for dental caries. But in our study cohort, all of these parameters did not affect dental caries formation. Low-molecular weight mucin contains 377 amino acids. The first 20 of these are located in the N-terminal domain and are very hydrophobic. It contains a central part, made of six tandem repeats of 23 amino acids that are rich in proline and hydroxylated amino acids, and having approximately 90-100 O-linked chains. A histatin-like domain with a leucine-zipper segment, followed by a moderately glycosylated region, constitute the N-terminal domain; a heavily glycosylated domain, and a second leucine-zipper segment for the C-terminal extremity. The distal regions of MUC7 do not exhibit any cysteine-rich domains, only two cysteine residues are present towards its N-terminal end. So far, MG2 has no sequence homology with any other mucins. The N-terminal region of the protein binds Streptococcus mutans (S. mutans). It also exhibits a candidacidal activity and, after cleavage, a subdomain of this region is microbicidal against a periodontal pathogen, Actinobacillus actinomycetemcomitans. Furthermore, a MUC7 20-mer displays potent killing activity against a variety of fungi and both gram-positive and gramnegative bacteria [4,11,12]. The two cysteine residues located in the N-terminal region of MUC7 seem to be directly implicated in these activities [12]. Low-molecular weight mucin has been reported to interact with several strains of streptococci by promoting their agglutination [13]. The N-terminal region of MG2 has a broad-spectrum fungicidal and bactericidal activity in vitro [14,15]. Low-molecular weight mucin peptides derived from the N-terminal of MG2 are the cationic anti-microbial peptides derived from the human low molecular weight salivary mucin, a component of innate immunity (the first-line of the host defense system against pathogens). Lowmolecular weight mucin (357 amino acid residues in saliva), protects the oral cavity from microbial infections through more general protective mechanisms rather than the direct killing of microorganisms [16]. It was shown that a 20 kDa MG2 fragment, containing the N-terminal region, was present in the saliva and suggested that cleavage of MG2 in vivo may lead to the fragments with microbicidal properties [17]. The MG2 20-mer, sub-domain of N- terminal domain, has been shown to be able to cross the fungal cell membrane and accumulate inside the cells, suggesting a possibility that MG2 peptides may also exert killing activity against S. mutans [18]. In some conditions, rather than killing the bacteria directly, they disturb cariogenic and periodontal pathogen activity by interacting with them, binding the bacteria via their cysteine residues within their N-terminal domain [19,20]. The peptides derived from the N-terminal region of MG2 present somewhat preferential antimicrobial activity against S. mutans. They also have an effect on in vitro formation and reduction of the preformed S. mutans biofilm [15]. We did not detect any statistically significant polymorphisms between caries and caries-free groups in the present study. There was one common SNP, affecting the amino acid at position 80, changing the natural amino acid asparagine to lysine. This SNP seemed to have no effect on dental caries in individuals, but seems to be an important polymorphism in the examined Turkish subjects. In conclusion, the SNP detected in this study may be a specific polymorphism effecting the Turkish population. Further studies with a larger number of individuals are necessary in order to clarify our findings. Declaration of Interest. The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.



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