Sinomenine, theophylline, cysteine, and levamisole: Comparisons of their kinetic effects on mineral formation induced by matrix vesicles

• Published in: Journal of inorganic biochemistry Vol. 104; no. 4; pp. 446 - 454
• Main Authors: Li, Lina, Buchet, René, Wu, Yuqing
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-04-2010; Elsevier
• Subjects: Adenosine Monophosphate - metabolism; Animals; Antirheumatic Agents - pharmacology; Biochemistry; Biochemistry, Molecular Biology; Calcification; Calcification, Physiologic - drug effects; Cartilage - chemistry; Cartilage - metabolism; Chick Embryo; Cysteine - pharmacology; Durapatite - metabolism; Extracellular Matrix - drug effects; Extracellular Matrix - metabolism; Humans; Levamisole - pharmacology; Life Sciences; Matrix vesicles; Mineral formation; Minerals - chemistry; Minerals - metabolism; Morphinans - pharmacology; Phosphates - metabolism; Phosphodiesterase Inhibitors - pharmacology; Sinomenine; Sinomenium acutum; Theophylline; Theophylline - pharmacology; Transport Vesicles - chemistry; Transport Vesicles - metabolism; Sinomenine; Calcification; Mineral formation; Matrix vesicles; Theophylline
• ISSN: 0162-0134; 1873-3344
• DOI: 10.1016/j.jinorgbio.2009.12.018

The effects of sinomenine (SIN, an alkaloid extracted from the Chinese medicinal plant
Sinomenium acutum used for centuries to treat rheumatic disease, including rheumatoid arthritis) on apatitic nucleation and matrix vesicle (MV)-induced mineral formation were studied and compared with those of cysteine, levamisole and theophylline. The possible roles of annexins and other ion transporters, such as proteins of the solute carrier family implicated in Ca
2+ and P
i influx are discussed.
The effects of sinomenine (SIN, an alkaloid extracted from the Chinese medicinal plant
Sinomenium acutum used for centuries to treat rheumatic disease, including rheumatoid arthritis) on apatitic nucleation and matrix vesicle (MV)-induced mineral formation were compared with those of cysteine, levamisole, and theophylline. We found that SIN was not an inhibitor of tissue non-specific alkaline phosphatase (TNAP), a marker of biological mineralization, but confirmed that cysteine, levamisole, and theophylline were. Further, none of these four molecules directly affected the nucleation of hydroxyapatite (HA) formation, in contrast to pyrophosphate (PP
i) which did. Incubation of 0.25–1.0
mM cysteine, theophylline, or levamisole with MVs in synthetic cartilage lymph (SCL) containing AMP and Ca
2+, but not inorganic phosphate (P
i), prolonged the induction time of mineral formation, apparently by inhibiting TNAP activity. SIN at the same levels neither inhibited TNAP activity nor affected the induction time of MV mineral formation. However, SIN did markedly delay MV-induced mineral formation in SCL containing P
i (instead of AMP) in a manner similar to theophylline, but to a lesser extent than levamisole. Cysteine did not delay, in fact it slightly accelerated MV-induced mineral formation in Pi-containing SCL. These findings suggest that levamisole, SIN and theophylline may directly affect Ca
2+ and/or P
i accretion during mineral formation; however, TNAP was not directly involved. The possible roles of annexins and other ion transporters, such as proteins of the solute carrier family implicated in Ca
2+ and P
i influx are discussed.