Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway.

doi:10.1016/j.ejphar.2014.03.009

中山醫學大學機構典藏 CSMUIR > 口腔醫學院 > 牙醫學系暨碩士班 > 期刊論文 > Item 310902500/10559

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/10559

Title:	Aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of pentose phosphate pathway.
Authors:	Su YF Yang, SH Lee, YH Wu, BC Huang, SC Liu, CM Chen, SL Pan, YF Chou, SS Chou, MY Yang HW
Contributors:	中山醫學大學
Keywords:	Adipogenesis;Aspirin;Aspirin (PubChem CID: 2244);Aspirin resistance;ERK 1/2 MAPK;Oil Red O (PubChem CID: 6046885);PD98059 (PubChem CID: 4713);Pentose phosphate pathway;Pifithrin-α (PubChem CID: 9929138);Tumor suppressor p53
Date:	2014
Issue Date:	2015-03-27T08:35:15Z (UTC)
ISSN:	0014-2999
Abstract:	Obesity has become a major public health problem of global significance. Today, aspirin remains the most commonly used medication for the treatment of pyrexia, pain, inflammation and antiplatelet. The present study aims at evaluating the possible existence of a putative p53-dependent pathway underlying the aspirin-induced inhibition of adipogenesis. Cell migration assay was identified by the ability to migrate through Transwell insert. Oil Red O staining was employed to quantify adipose accumulation. The concentration of glucose and triglyceride were measured by using assay kits. The expression levels of several master regulatory molecules controlling various signal pathways were monitored using the immunoblotting techniques. Aspirin significantly inhibited preadipocyte migration and adipose accumulation. The p53-p21 signaling and the expression of differentiation marker glycerol-3-phosphate dehydrogenase were increased in a dose-dependent manner. It indicated that aspirin induced adipocyte differentiation through p53-p21 pathway. The oncogenic ERK 1/2 MAPK signaling was induced, whereas, the expression of adipogenic markers peroxisome proliferator-activated receptor γ (PPARγ), adipocyte fatty acid-binding protein (A-FABP) and inflammatory factors cyclooxygenase-2 (Cox-2), tumor necrosis factor α (TNFα) and inducible nitric oxide synthase (iNOS) were inhibited. Aspirin negatively regulated the pentose phosphate pathway (PPP) by inhibiting the expression of rate-limiting enzyme glucose-6-phosphate dehydrogenase. Knockdown the expression of oncogenic ERK 1/2 MAPK by using 10 μM PD98059 significantly increased triglyceride synthesis, adipose accumulation and activated PPP, however, decreased glucose uptake. Diverted the glucose flux to PPP, rather than increased glucose uptake, was associated with adipogenesis. Down-regulated the expression of tumor suppressor p53 by 10 μM pifithrin-α (PFTα) alone had no effect on adipose accumulation. However, administration of aspirin accompanied with PFTα abolished aspirin-induced inhibition of adipogenesis. We demonstrated that aspirin-induced inhibition of adipogenesis was p53-dependent and associated with inactivation of PPP. Blockade PPP may be a novel strategy for obesity prevention and therapy. Moreover, when use aspirin in therapeutic strategy, the p53 status should be considered.
URI:	https://ir.csmu.edu.tw:8080/ir/handle/310902500/10559 http://dx.doi.org/10.1016/j.ejphar.2014.03.009
Relation:	Eur J Pharmacol. 2014 Sep 5;738:101-10.
Appears in Collections:	[牙醫學系暨碩士班] 期刊論文

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