N-methyl-N-nitrosourea-induced apoptosis of photoreceptor cells in Sprague-Dawley rats via nuclear factor-κB
- Author:
- No author available
- Journal Title:
- CHINESE MEDICAL JOURNAL
- Issue:
- 13
- DOI:
- No doi available
- Key Word:
- methylnitrosourea;photoreceptors;apoptosis;nuclear factor-kappa B
Abstract： Background Previous studies have showed that photooxidative stress can lead to down-modulation of nuclear factor-κappa B (NF-κB) activity causing apoptosis of cultured photoreceptor cells. This study aimed at investigating whether NF-κB was involved in photoreceptor cells apoptosis induced by N-methyl-N-nitrosourea (MNU) in rats.Methods A single intraperitoneal injection of 60 mg/kg MNU was given to 50-day-old female rats. At different intervals after MNU treatment,the animals were sacrificed. Retinal damage was examined by a light microscope. The apoptotic index of the photoreceptor cells was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL). NF-κB was analysed by Western blot and Transcriptin Factor Assay Kits. Results The pyknosis of the photoreceptor nuclei and the disorientation of the outer segment of the photoreceptor layer was seen after MNU treatment for 24 hours. The outer nuclear layer and photoreceptor layer were almost completely lost at 7 days. Photoreceptor cells apoptosis reached the peaked value at 24 hours. In apoptotic cascade, the protein levels of NF-κB p65 were only detected after MNU treatment for 12 and 24 hours in the nucleus. Conversely, the amounts of IκBα were markedly increased in the cytoplasm as well as in the nucleus. The activity of NF-κB p65 in the nucleus was down-modulated in the end.Conclusions MNU-induced photoreceptor cell destruction was attributed to the apoptotic process by down-regulating the activation of NF-κB p65.
- [1]Aggarwal BB.,Takada Y.,Singh S..Identification of a p65 peptide that selectively inhibits NF-kappa B activation induced by various inflammatory stimuli and its role in down-regulation of NF-kappa B-mediated gene expression and up-regulation of apoptosis[J].2004,279(15).
- [2]A A, Beg,W C, Sha,R T, Bronson,etc.Embryonic lethality and liver degeneration in mice lacking the RelA component of NF-kappa B.[J].1995,376(6536).
- [3]M O, Tso,C, Zhang,A S, Abler,etc.Apoptosis leads to photoreceptor degeneration in inherited retinal dystrophy of RCS rats.[J].1994,35.
- [4]Charlotte E Remé,Christian Grimm,Farhad Hafezi,etc.Apoptotic cell death in retinal degenerations[J].1998,17(4).
- [5]Jian-ya ZHOU,Fa-di TANG,Guo-gen MAO,etc.Effect of α-pinene on nuclear translocation of NF-κB in THP-1 cells[J].2004,(4).
- [6]Gorlich,D,Kutay,U.Transport between the cell nucleus and the cytoplasm.[J].1999,15.
- [7]Chun MH,Kim DH,Yoon SK,etc.Failure to activate NF-kappaB promotes apoptosis of retinal ganglion cells following optic nerve transection.[J].2000,883(1).
- [8]Grilli, Mariagrazia,Pizzi, Marina.Neuroprotection by aspirin and sodium salicylate through blockade of NF-kB activation.[J].1996,274(5291).
- [9]F F, Davidson,H, Steller.Blocking apoptosis prevents blindness in Drosophila retinal degeneration mutants.[J].1998,391(6667).
- [10]A A, Beg,D, Baltimore.An essential role for NF-kappaB in preventing TNF-alpha-induced cell death.[J].1996,274.
- [11]J, Cinatl,M, Bittoova,S, Margraf,etc.Cytomegalovirus infection decreases expression of thrombospondin-1 and -2 in cultured human retinal glial cells: effects of antiviral agents.[J].2000,182.
- [12]K, Yoshizawa,H, Nambu,J, Yang,etc.Mechanisms of photoreceptor cell apoptosis induced by N-methyl-N-nitrosourea in Sprague-Dawley rats.[J].1999,79.
- [13]Taomoto,M,Nambu,H,Senzaki,H,etc.Retinal degeneration induced by N-methyl-N-nitrosourea in Syrian golden hamsters.[J].1998,236(9).
- [14]Cun-Yu Wang,Marty W. Mayo,Robert G. Korneluk,etc.NF-κB Antiapoptosis: Induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to Suppress Caspase-8 Activation[J].1998,281 (5383).
- [15]Holler N.,Irmler M.,Martinon F.,etc.The caspase-8 inhibitor FLIP promotes activation of NF-kappa B and Erk signaling pathways[J].2000,10(11).
- [16]Gaynor RB,Yamamoto Y.Therapeutic potential of inhibition of the NF-kappaB pathway in the treatment of inflammation and cancer.[J].2001,107(2).
- [17]H, Ogino,M, Ito,K, Matsumoto,etc.Retinal degeneration induced by N-methyl-N-nitrosourea and detection of 7-methyldeoxyguanosine in the rat retina.[J].1993,21.
- [18]Aggarwal BB,Agarwal N,Chaturvedi MM,etc.Photo-oxidative stress down-modulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells.[J].1999,274(6).
- [19]Khalil AK,Inomata H,Yoshida S,etc.Role of NF-kappaB-mediated interleukin-8 expression in intraocular neovascularization.[J].1998,39(7).
- [20]K, Yuge,H, Nambu,H, Senzaki,etc.N-methyl-N-nitrosourea-induced photoreceptor apoptosis in the mouse retina.[J].1900,10(5).
- [21]M, Nakajima,K, Yuge,H, Senzaki,etc.Photoreceptor apoptosis induced by a single systemic administration of N-methyl-N-nitrosourea in the rat retina.[J].1996,148.
- [22]Carter, Bruce D.,Kaltschmidt, Christian.Selective activation of NF-kappaB by nerve growth factor through the neurotrophin receptor p75.[J].1996,272(5261).
- [23]Kaltschmidt B,Uherek M,Wellmann H,etc.Inhibition of NF-kappaB potentiates amyloid beta-mediated neuronal apoptosis.[J].1999,96(16).
- [24]Hasebe Y,Thomson LR,Dorey CK.Pentoxifylline inhibition of vasculogenesis in the neonatal rat retina.[J].2000,41(9).
- [25]Baldwin AS Jr.The NF-kappa B and I kappa B proteins: new discoveries and insights.[J].1996,14.
- [26]W X, Zong,L C, Edelstein,C, Chen,etc.The prosurvival Bcl-2 homolog Bfl-1/A1 is a direct transcriptional target of NF-kappaB that blocks TNFalpha-induced apoptosis.[J].1999,13.