Prolidase dependent inhibition of collagen biosynthesis in Chinese hamster ovary cells.
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. It was previously 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, and therefore require addition of free proline or glicyl-proline (converted to glycine and proline) for growth. We have found that 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 signalling induced by growth factors, since no changes were observed in expression of AKT in CHO cells incubated with Ni(II). The results presented provide evidence for important role of prolidase in collagen biosynthesis.
Miltyk
Wojciech
W
Department of Pharmaceutical Analysis, Medical University in Bialystok Kilińskiego 1 15-089 Bialystok, Poland.
Surazynski
Arkadiusz
A
Grabowska
Joanna
J
Palka
Jerzy A
JA
D000818:Animals; D016466:CHO Cells; D003094:Collagen / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004150:Dipeptidases / Q000378:metabolism / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D006909:Hydroxyproline / Q000737:chemistry; D016023:Integrins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008954:Models, Biological; D009532:Nickel / Q000737:chemistry; D014158:Transcription, Genetic
D016023:Integrins; D009532:Nickel; D003094:Collagen; D004150:Dipeptidases; C022449:proline dipeptidase; D006909:Hydroxyproline