Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1)

Toshiyuki Chikuma, Yoko Ishii, Takeshi Kato, Noriyoshi Kurihara, Yoshiyuki Hakeda, Masayoshi Kumegawa

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 μg/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.

Original languageEnglish (US)
Pages (from-to)4319-4324
Number of pages6
JournalBiochemical Pharmacology
Volume36
Issue number24
DOIs
StatePublished - Dec 15 1987
Externally publishedYes

Fingerprint

thimet oligopeptidase
Chlorpromazine
prolyl oligopeptidase
Peptide Hydrolases
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
Aminopeptidases
Leucyl Aminopeptidase
Collagen
Degradation
Peptides
Microbial Collagenase
Derivatives
Osteoblasts
Enzyme activity

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1). / Chikuma, Toshiyuki; Ishii, Yoko; Kato, Takeshi; Kurihara, Noriyoshi; Hakeda, Yoshiyuki; Kumegawa, Masayoshi.

In: Biochemical Pharmacology, Vol. 36, No. 24, 15.12.1987, p. 4319-4324.

Research output: Contribution to journalArticle

Chikuma, Toshiyuki ; Ishii, Yoko ; Kato, Takeshi ; Kurihara, Noriyoshi ; Hakeda, Yoshiyuki ; Kumegawa, Masayoshi. / Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1). In: Biochemical Pharmacology. 1987 ; Vol. 36, No. 24. pp. 4319-4324.
@article{a0a48e47a1b9490e95421ef29af70a2a,
title = "Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1)",
abstract = "The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 μg/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.",
author = "Toshiyuki Chikuma and Yoko Ishii and Takeshi Kato and Noriyoshi Kurihara and Yoshiyuki Hakeda and Masayoshi Kumegawa",
year = "1987",
month = "12",
day = "15",
doi = "10.1016/0006-2952(87)90678-2",
language = "English (US)",
volume = "36",
pages = "4319--4324",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "24",

}

TY - JOUR

T1 - Effect of chlorpromazine on pz-peptidase and several other peptidase activities in cloned osteoblastic cells (MC3T3-E1)

AU - Chikuma, Toshiyuki

AU - Ishii, Yoko

AU - Kato, Takeshi

AU - Kurihara, Noriyoshi

AU - Hakeda, Yoshiyuki

AU - Kumegawa, Masayoshi

PY - 1987/12/15

Y1 - 1987/12/15

N2 - The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 μg/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.

AB - The effect of chlorpromazine (CPZ) on the degradation of collagen and non-collagenous peptides in clonal osteoblastic MC3T3-E1 cells was investigated by measuring the activities of PZ-peptidase, collagenase-like peptidase (CL-peptidase), dipeptidyl-aminopeptidase (DAP), leucine aminopeptidase (LAP) (EC 3.4.11.1), and post-proline cleaving enzyme (PPCE) (EC 3.4.21.26). CPZ increased PZ-peptidase and CL-peptidase activities in a dose-related fashion, but it had no effect on LAP and PPCE activities in the cells. CPZ (10 μg/ml) enhanced the specific activities of PZ-peptidase, CL-peptidase, and DAP for 72 hr after the start of CPZ stimulation; in particular, about a 3.3-fold increase of PZ-peptidase activity was observed at 12 hr of culture. Furthermore, other phenothiazine derivatives specifically enhanced the PZ-peptidase, CL-peptidase, and DAP activities as well as CPZ. Since PZ-peptidase, CL-peptidase, and DAP, involved in the degradation of collagen peptides, were induced significantly by CPZ (and/or other phenothiazine derivatives) in comparison with LAP and PPCE, involved in the degradation of non-collagenous peptides, these results show that CPZ specifically stimulated collagen catabolism by inducing the collagen-catabolizing enzymes. In addition, CPZ specifically inhibited collagen synthesis in clonal osteoblasts.

UR - http://www.scopus.com/inward/record.url?scp=0023568347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023568347&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(87)90678-2

DO - 10.1016/0006-2952(87)90678-2

M3 - Article

VL - 36

SP - 4319

EP - 4324

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 24

ER -