Phosphatidylcholine induces apoptosis of 3T3-L1 adipocytes

Journal of Biomedical Science

Dong-Seok Kim¹  Ji Hoon Jeong³  Yoosik Yoon²  Nyoun Soo Kwon¹  Kwang Jin Baek¹  Hye-Young Yun¹  Su Yeon Kim¹  Jong-Hyuk Lee³  Hailan Li¹ 

[1] Departments of Biochemistry, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea;Departments of Microbiology, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea;Departments of Pharmacology, Chung-Ang University College of Medicine, 221 Heukseok-dong, Dongjak-gu, Seoul 156-756, Republic of Korea

关键词: PPC;    mesotherapy;    caspases;    apoptosis;    adipocytes;   

Others  :  1146730
DOI  :  10.1186/1423-0127-18-91

 received in 2011-09-01, accepted in 2011-12-07,  发布年份 2011

【 摘 要 】

Background

Phosphatidylcholine (PPC) formulation is used for lipolytic injection, even though its mechanism of action is not well understood.

Methods

The viability of 3T3-L1 pre-adipocytes and differentiated 3T3-L1 cells was measured after treatment of PPC alone, its vehicle sodium deoxycholate (SD), and a PPC formulation. Western blot analysis was performed to examine PPC-induced signaling pathways.

Results

PPC, SD, and PPC formulation significantly decreased 3T3-L1 cell viability in a concentration-dependent manner. PPC alone was not cytotoxic to CCD-25Sk human fibroblasts at concentrations <1 mg/ml, whereas SD and PPC formulation were cytotoxic. Western blot analysis demonstrated that PPC alone led to the phosphorylation of the stress signaling proteins, such as p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, and activated caspase-9, -8, -3 as well as cleavage of poly(ADP-ribose) polymerase. However, SD did not activate the apoptotic pathways. Instead, SD and PPC formulation induced cell membrane lysis, which may lead to necrosis of cells.

Conclusions

PPC results in apoptosis of 3T3-L1 cells.

【 授权许可】

   
2011 Li et al; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Pistor M: What is mesotherapy? Chir Dent Fr 1976, 46:59-60.
• [2]Young VL: Lipostabil: the effect of phosphatidylcholine on subcutaneous fat. Aesthet Surg J 2003, 23:413-417.
• [3]Rotunda AM, Kolodney MS: Mesotherapy and phosphatidylcholine injections: historical clarification and review. Dermatol Surg 2006, 32:465-480.
• [4]Ablon G, Rotunda AM: Treatment of lower eyelid fat pads using phosphatidylcholine: clinical trial and review. Dermatol Surg 2004, 30:422-427. discussion 428
• [5]Rittes PG: The use of phosphatidylcholine for correction of localized fat deposits. Aesthetic Plast Surg 2003, 27:315-318.
• [6]Klein SM, Schreml S, Nerlich M, Prantl L: In vitro studies investigating the effect of subcutaneous phosphatidylcholine injections in the 3T3-L1 adipocyte model: lipolysis or lipid dissolution? Plast Reconstr Surg 2009, 124:419-427.
• [7]Gupta A, Lobocki C, Singh S, Robertson M, Akadiri OA, Malhotra G, Jackson IT: Actions and comparative efficacy of phosphatidylcholine formulation and isolated sodium deoxycholate for different cell types. Aesthetic Plast Surg 2009, 33:346-352.
• [8]Salti G, Ghersetich I, Tantussi F, Bovani B, Lotti T: Phosphatidylcholine and sodium deoxycholate in the treatment of localized fat: a double-blind, randomized study. Dermatol Surg 2008, 34:60-66. discussion 66
• [9]Moessinger C, Kuerschner L, Spandl J, Shevchenko A, Thiele C: Human lysophosphatidylcholine acyltransferases 1 and 2 are located in lipid droplets where they catalyze the formation of phosphatidylcholine. J Biol Chem 2011, 286:21330-21339.
• [10]Vance JE, Vance DE: Phospholipid biosynthesis in mammalian cells. Biochem Cell Biol 2004, 82:113-128.
• [11]Aleynik SI, Lieber CS: Polyenylphosphatidylcholine corrects the alcohol-induced hepatic oxidative stress by restoring s-adenosylmethionine. Alcohol Alcohol 2003, 38:208-212.
• [12]Harayama T, Shindou H, Shimizu T: Biosynthesis of phosphatidylcholine by human lysophosphatidylcholine acyltransferase 1. J Lipid Res 2009, 50:1824-1831.
• [13]Sakakima Y, Hayakawa A, Nakao A: Phosphatidylcholine induces growth inhibition of hepatic cancer by apoptosis via death ligands. Hepatogastroenterology 2009, 56:481-484.
• [14]Kopera D, Binder B, Toplak H: Intralesional lipolysis with phosphatidylcholine for the treatment of lipomas: pilot study. Arch Dermatol 2006, 142:395-396.
• [15]Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW, Allen K, Lopes M, Savoye M, Morrison J, Sherwin RS, Caprio S: Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004, 350:2362-2374.
• [16]Sorisky A, Magun R, Gagnon AM: Adipose cell apoptosis: death in the energy depot. Int J Obes Relat Metab Disord 2000, 24(Suppl 4):S3-7.
• [17]Levine JA, Jensen MD, Eberhardt NL, O'Brien T: Adipocyte macrophage colony-stimulating factor is a mediator of adipose tissue growth. J Clin Invest 1998, 101:1557-1564.
• [18]Xiao Y, Yuan T, Yao W, Liao K: 3T3-L1 adipocyte apoptosis induced by thiazolidinediones is peroxisome proliferator-activated receptor-gamma-dependent and mediated by the caspase-3-dependent apoptotic pathway. FEBS J 2010, 277:687-696.
• [19]Hengartner MO: The biochemistry of apoptosis. Nature 2000, 407:770-776.
• [20]Shah GM, Shah RG, Poirier GG: Different cleavage pattern for poly(ADP-ribose) polymerase during necrosis and apoptosis in HL-60 cells. Biochem Biophys Res Commun 1996, 229:838-844.
• [21]Casiano CA, Ochs RL, Tan EM: Distinct cleavage products of nuclear proteins in apoptosis and necrosis revealed by autoantibody probes. Cell Death Differ 1998, 5:183-190.
• [22]Wu BT, Hung PF, Chen HC, Huang RN, Chang HH, Kao YH: The apoptotic effect of green tea (-)-epigallocatechin gallate on 3T3-L1 preadipocytes depends on the Cdk2 pathway. J Agric Food Chem 2005, 53:5695-5701.
• [23]Rotunda AM, Suzuki H, Moy RL, Kolodney MS: Detergent effects of sodium deoxycholate are a major feature of an injectable phosphatidylcholine formulation used for localized fat dissolution. Dermatol Surg 2004, 30:1001-1008.
• [24]Duncan DI, Palmer M: Fat reduction using phosphatidylcholine/sodium deoxycholate injections: standard of practice. Aesthetic Plast Surg 2008, 32:858-872.
• [25]Rotunda AM, Ablon G, Kolodney MS: Lipomas treated with subcutaneous deoxycholate injections. J Am Acad Dermatol 2005, 53:973-978.
• [26]Hasengschwandtner F: Phosphatidylcholine treatment to induce lipolysis. J Cosmet Dermatol 2005, 4:308-313.
• [27]Fukunaga K, Hossain Z, Takahashi K: Marine phosphatidylcholine suppresses 1,2-dimethylhydrazine-induced colon carcinogenesis in rats by inducing apoptosis. Nutr Res 2008, 28:635-640.
• [28]Cheng Y, Zhao Q, Liu X, Araki S, Zhang S, Miao J: Phosphatidylcholine-specific phospholipase C, p53 and ROS in the association of apoptosis and senescence in vascular endothelial cells. FEBS Lett 2006, 580:4911-4915.
• [29]Baez JM, Tabas I, Cohen DE: Decreased lipid efflux and increased susceptibility to cholesterol-induced apoptosis in macrophages lacking phosphatidylcholine transfer protein. Biochem J 2005, 388:57-63.
• [30]Wagner EF, Nebreda AR: Signal integration by JNK and p38 MAPK pathways in cancer development. Nat Rev Cancer 2009, 9:537-549.
• [31]Fulda S: Caspase-8 in cancer biology and therapy. Cancer Lett 2009, 281:128-133.
• [32]Jeong YM, Li H, Kim SY, Park WJ, Yun HY, Baek KJ, Kwon NS, Jeong JH, Myung SC, Kim DS: Photo-activated 5-hydroxyindole-3-acetic acid induces apoptosis of prostate and bladder cancer cells. J Photochem Photobiol B 2011, 103:50-56.
• [33]Denning TL, Takaishi H, Crowe SE, Boldogh I, Jevnikar A, Ernst PB: Oxidative stress induces the expression of Fas and Fas ligand and apoptosis in murine intestinal epithelial cells. Free Radic Biol Med 2002, 33:1641-1650.
• [34]Facchinetti F, Furegato S, Terrazzino S, Leon A: H(2)O(2) induces upregulation of Fas and Fas ligand expression in NGF-differentiated PC12 cells: modulation by cAMP. J Neurosci Res 2002, 69:178-188.
• [35]Watanapokasin R, Jarinthanan F, Nakamura Y, Sawasjirakij N, Jaratrungtawee A, Suksamrarn S: Effects of alpha-mangostin on apoptosis induction of human colon cancer. World J Gastroenterol 2011, 17:2086-2095.
• [36]Kim ND, Im E, Yoo YH, Choi YH: Modulation of the cell cycle and induction of apoptosis in human cancer cells by synthetic bile acids. Curr Cancer Drug Targets 2006, 6:681-689.