title: Acrylamide induces mitochondrial dysfunction and apoptosis in BV-2 microglial cells.
abstract: Acrylamide (ACR), a potent neurotoxin, can be produced during food processing at high temperature. This study examined the redox-dependent apoptotic and inflammatory responses of ACR in an immortalized mouse microglia cell line BV2. The exposure of BV2 cells to ACR reduced cell viability and induced apoptosis in a concentration-dependent manner. ACR impaired cell energy metabolism by decreasing mitochondrial respiration, anaerobic glycolysis, and lowering expression of the complex I, III, and IV subunits. Mitochondrial dysfunction was associated with a decrease of the mitochondrial membrane potential and the Bcl-2/Bax ratio, thus resulting in activation of the mitochondrion-driven apoptotic signaling. This was accompanied by (a) the modulation of redox-sensitive signaling, suppressed Akt activation and increased JNK and p38 activation, and (b) increased expression of NFκB and downstream inducible nitric oxide synthase (iNOS) and nitric oxide generation, thus supporting indirectly a proinflammatory effect of ACR. Nrf2 expression was also increased but not its translocation to the nucleus. Expectedly, the electrophilic attack of ACR on GSH resulted in substantial loss of GSH with a minor GSSG formation. These changes in the cell׳s redox status elicited by ACR resulted in increased H2O2 formation. The changes in mitochondrial functionality and complex subunit expression caused by ACR were reversed by N-acetyl-L-cysteine (NAC). Likewise, NAC restored the cell׳s redox status by increasing GSH levels with concomitant attenuation of H2O2 generation; these effects resulted in decreased apoptotic cell death and inflammatory responses. ACR-mediated mitochondrial dysfunction along with a more oxidized redox status seems to be critical events leading to activation of the intrinsic apoptotic pathway and inflammatory responses.
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China; Pharmacology & Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA, USA.
authors: Zhigang
authors: Z
authors: Liu
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China.
authors: Ge
authors: G
authors: Song
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China.
authors: Chen
authors: C
authors: Zou
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China.
authors: Gongguan
authors: G
authors: Liu
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China.
authors: Wanqiang
authors: W
authors: Wu
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China.
authors: Tian
authors: T
authors: Yuan
authors: College of Food Science and Engineering, Northwest A&F University, Yangling, China. Electronic address: xueboliu@aliyun.com.
authors: Xuebo
authors: X
authors: Liu
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D020935:MAP Kinase Signaling System; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D010101:Oxygen Consumption
chemical_list: D020106:Acrylamide
keywords: Acrylamide; Apoptosis; Energy metabolism; Microglia; Mitochondrial dysfunction; Redox signaling