Characterization of cationic amino acid transporters (hCATs) 1 and 2 in human skin

• Published in: Histochemistry and cell biology Vol. 129; no. 3; pp. 321 - 329
• Main Authors: Jaeger, Kristin, Paulsen, Friedrich, Wohlrab, Johannes
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01-03-2008; Springer Nature B.V
• Subjects: Adult; Amino acids; Arginine - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Cationic Amino Acid Transporter 1 - drug effects; Cationic Amino Acid Transporter 1 - genetics; Cationic Amino Acid Transporter 1 - metabolism; Cationic Amino Acid Transporter 2 - drug effects; Cationic Amino Acid Transporter 2 - genetics; Cationic Amino Acid Transporter 2 - metabolism; Cell Biology; Cells, Cultured; Cellular biology; Comparative studies; Developmental Biology; Dose-Response Relationship, Drug; Female; Histology; Humans; Immunohistochemistry; Male; Middle Aged; Original Paper; Ornithine - pharmacology; Psoriasis; Psoriasis - metabolism; Psoriasis - pathology; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - drug effects; RNA, Messenger - genetics; Skin - metabolism; Young Adult; Human; Cationic amino acid transporter; Psoriasis; Native human epidermal keratinocytes
• ISSN: 0948-6143; 1432-119X
• DOI: 10.1007/s00418-007-0367-6

In the present study, we characterized the distribution of human cationic amino acid transporters 1 (hCAT1) and 2 (hCAT2) in healthy skin and compared it to psoriatic skin lesions by means of immunohistochemistry. Moreover, we tested the hypothesis that
l
-arginine and
l
-ornithine influence the expression and synthesis of hCAT1 and hCAT2 in cell culture experiments by means of real-time-PCR and Western blot. Immunohistochemical comparison between healthy and psoriatic skin revealed a decreased amount of hCAT1, especially in the stratum granulosum of psoriatic skin; the distribution pattern of hCAT2 was not significantly affected in psoriatic skin. Cell culture experiments showed that supraphysiological concentrations of 15 mM
l
-arginine (72 h) lead to a significant increase of the hCAT1-mRNA and protein expression, whereas other concentrations had no significant influence. In contrast,
l
-arginine concentrations of 2 mM led to a significant increase of the hCAT2B mRNA-expression after 24 h. However, 48 and 72 h revealed no significant changes and high concentrations (15 mM
l
-arginine) led to a significant downregulation of the hCAT2B transporter over all time points analyzed.
l
-ornithine had no effect on the hCAT1 expression of mRNA and protein level. On the other hand the expression of hCAT2B was significantly up regulated at a 5-mM concentration of
l
-ornithine at all analyzed time points. Other concentrations had no effect. For the first time, the findings yield data about hCAT1 and hCAT2 on protein-level and suggest that
l
-arginine is a worthwhile object of studies, which investigated
l
-arginine as a possible therapeutic agent to reduce psoriatic symptoms.