Complement 3 (C3) through its interaction with factors B and D (adipsin) generates C3a. In the human body, C3a is rapidly cleaved by carboxypeptidase B or carbxyopeptidase N, that remove the carboxyl-terminal arginine to generate C3adesArg. Thus, most of plasmatic C3a is present in C3adesArg form. C3adesArg is more commonly named ASP or acylation-stimulating-protein due to its marked stimulating action on triacylglycerol synthesis in human adipocytes and skin fibroblasts. ASP is also known for its augmentation of glucose transport and inhibiting action on hormone-sensitive lipase. Because of these actions, it is linked to the pathogenesis of obesity, having been demonstrated to be present at increased levels in patients with obesity, diabetes mellitus type 2 and coronary artery disease.
ASP lis a ligand for C5L2, a G-protein-coupled receptor.
The view of C3a/C3adesArg as an acylation stimulating activity is not universally accepted. The evidence is discussed in a recent review.
References
- Baldo et al. 1993, pp. 1543–1547
- Cianflone et al., pp. 426–430
- (Sniderman, Maslowska & Cianflone 2000, pp. 291–296)
- Maslowska et al. 1999, pp. 679–686
- Koistinen et al. 2001, pp. 1034–1039
- Cianflone et al. 1997, pp. 1239–1244
- Cui et al. 2009, pp. 3207–3217
- Klos A, Wende E, Wareham KJ, Monk PN (2013). "International Union of Pharmacology. LXXXVII. Complement peptide C5a, C4a, and C3a receptors". Pharmacol. Rev. 65 (1): 500–43. doi:10.1124/pr.111.005223. PMID 23383423.
Further reading
- Baldo, A; Sniderman, A D; St-Luce, S; Avramoglu, R K; Maslowska, M; Hoang, B; Monge, J C; Bell, A; Mulay, S; Cianflone, K (1993). "The adipsin-acylation stimulating protein system and regulation of intracellular triglyceride synthesis". Journal of Clinical Investigation. 92 (3): 1543–1547. doi:10.1172/JCI116733. PMC 288301. PMID 8376604.
- Cianflone, Katherine M.; Sniderman, Allan D.; Walsh, Mark J.; Vu, Hai T.; Gagnon, Jean; Rodriguez, Miguel A. (1989). "Purification and Characterization of Acylation Stimulating Protein". The Journal of Biological Chemistry. 264 (1): 426–30. doi:10.1016/S0021-9258(17)31275-9. PMID 2909530.
- Cianflone, K.; Zhang, XJ; Genest Jr, J; Sniderman, A (July 1997). "Plasma acylation-stimulating protein in coronary artery disease". Arterioscler Thromb Vasc Biol. 17 (7): 1239–44. doi:10.1161/ATVB.17v07.1239. PMID 9261252.
- Cui, Wei; Lapointe, Marc; Gauvreau, Danny; Kalant, David; Cianflone, Katherine (October 2009). "Recombinant C3adesArg/acylation stimulating protein (ASP) is highly bioactive: a critical evaluation of C5L2 binding and 3T3-L1 adipocyte activation". Mol Immunol. 46 (16): 3207–17. doi:10.1016/j.molimm.2009.08.013. PMID 19767107.
- Sniderman, Allan D.; Maslowska, Magdalena; Cianflone, Katherine (2000). "Of mice and men (and women) and the acylation-stimulating protein pathway". Current Opinion in Lipidology. 11 (3): 291–6. doi:10.1097/00041433-200006000-00010. PMID 10882345.
- Maslowska, M; Vu, H; Phelis, S; Sniderman, AD; Rhode, BM; Blank, D; Cianflone, K (1999). "Plasma acylation stimulating protein, adipsin and lipids in non-obese and obese populations". European Journal of Clinical Investigation. 29 (8): 679–86. doi:10.1046/j.1365-2362.1999.00514.x. PMID 10457151. S2CID 19694467.
- Koistinen, Heikki A.; Vidal, Hubert; Karonen, Sirkka-Liisa; Dusserre, Eric; Vallier, Paulette; Koivisto, Veikko A.; Ebeling, Pertti (2001). "Plasma Acylation Stimulating Protein Concentration and Subcutaneous Adipose Tissue C3 mRNA Expression in Nondiabetic and Type 2 Diabetic Men". Arteriosclerosis, Thrombosis, and Vascular Biology. 21 (6): 1034–9. doi:10.1161/01.atv.21.6.1034. PMID 11397716.