Enhancement of gene expression by a peptide p(CHWPR) produced by Bifidobacterium lactis BB-12.
Recently, probiotics, including Bifidobacterium, Lactobacillus, and Enterococcus, among other organisms, have been clinically applied for their enhancing effects on defense mechanisms. It is reported that gene expression in somatic cells can be activated by autoinducers, which are hormone-like molecules produced in a microbial QS system. In the present study, based on a hypothesis that a low-molecular substance related to the QS system is involved in the probiotics effects of Bifidobacterium, we intended to extract the low-molecular substance. As a result, we successfully isolated the peptide p(CHWPR), which was composed of five amino acids including Cys, His, Trp, Pro, and Arg, and found that the peptide was produced in the stationary phase of bacterial growth and that it could enhance the gene expression of oxalyl-CoA decarboxylase (Oxc). p(CHWPR) enhanced the gene expression of c-myc and interleukin (IL)-6 in an established cell line, HL-60. We demonstrated that p(CHWPR) penetrates the cell membrane and binds specifically to RORgamma, which is a cytosolic nuclear receptor. This suggests that RORgamma bound to p(CHWPR) would bind to promoter regions of the c-myc gene. Furthermore, we found that p(CHWPR) also bound to a transcriptional avtivation subunit, CRSP70; this suggests that p(CHWPR), RORgamma, and CRSP70 in combination enhance transcription activity.
Mitsuma
Takashi
T
Department of Medical Technology, School of Health Science, Faculty of Medicine, Niigata University, Niigata, Japan. hiranosg@clg.niigata-u.ac.jp
Odajima
Hiroko
H
Momiyama
Zyunko
Z
Watanabe
Kana
K
Masuguchi
Misako
M
Sekine
Takashi
T
Shidara
Satoshi
S
Hirano
Shigeki
S
D001426:Bacterial Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D001644:Bifidobacterium / Q000378:metabolism*; D002262:Carboxy-Lyases / Q000096:biosynthesis*; D002460:Cell Line; D005786:Gene Expression Regulation; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010455:Peptides / Q000302:isolation & purification / Q000494:pharmacology*; D011485:Protein Binding; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism
D001426:Bacterial Proteins; C117286:CRSP protein, human; D015850:Interleukin-6; C489427:MYC protein, human; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D010455:Peptides; D016271:Proto-Oncogene Proteins c-myc; C539900:RORC protein, human; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D015534:Trans-Activators; D002262:Carboxy-Lyases; C059418:oxalyl CoA decarboxylase