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Journal of Biochemistry Advance Access published online on June 11, 2008

Journal of Biochemistry, doi:10.1093/jb/mvn083
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© 2008 The Japanese Biochemical Society

Prolidase dependent inhibition of collagen biosynthesis in Chinese hamster ovary cells.

Wojciech Miltyk#, Arkadiusz Surazynski*, Joanna Grabowska* and Jerzy A. Palka*,{ddagger}

#Department of Pharmaceutical Analysis, Medical University in Bialystok, Kilinskiego 1, 15-089 Bialystok
*Department of Medicinal Chemistry, Medical University in Bialystok, Kilinskiego 1, 15-089 Bialystok

{ddagger}Correspondence address: Prof. Jerzy A. Palka, Ph.D., Department of Medicinal Chemistry, Medical University in Bialystok, Kilinskiego 1, 15-089 Bialystok, Poland. Phone: (48) (85) 748-5706; fax: (48) (85) 879-5703; e-mail: pal{at}umwb.edu.pl

Received February 18, 2008; Accepted June 8, 2008


   Abstract

Summary

Collagen is responsible for maintenance of connective tissue integrity and through interaction with integrin receptors may participate in regulation of numerous physiological and pathological processes. An important role in collagen biosynthesis plays prolidase. Previously was found that nickel chloride inhibited prolidase activity in Chinese hamster ovary cells (CHO-C9). The cells lack any detectable ornithine aminotransferase and P5C synthase activities, therefore require addition of free proline or glicyl-proline (converted to glycine and proline) for growth. We have found Ni(II) contributed to decrease in collagen and hydroxyproline content in CHO cells incubated with Gly-Pro, whereas it had no effect on hydroxyproline content in the cells incubated with proline. Decrease in collagen content was not related to decrease in type I collagen mRNA level suggesting regulation of this process at post-transcriptional level. However decrease in expression of Sos and phosphorylated MAP-kinases were found in the cells growing in the presence of Gly-Pro and Ni(II). Decrease in the expression of these proteins was not related to inhibition of signaling induced by growth factors, since no changes were observed in expression of AKT in CHO cells incubated with Ni(II). The presented results provide evidence for important role of prolidase in collagen biosynthesis.

Key Words: collagen metabolism, integrin signaling, nickel, prolidase


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