Abstract
Aim:
To evaluate the effect of tetramethylpyrazine (TMP) injection on retinal damage induced by N-methyl-N-nitrosourea (MNU) in rats and on nuclear factor-kappa B (NF-κB) family members.
Methods:
Female Sprague-Dawley (SD) rats were randomly divided into groups: (i), control group; (ii), model group; and (iii), TMP-injection groups, in which the rats were subdivided into 40 mg/kg, 80 mg/kg and 160 mg/kg groups. Drugs were injected ip into 47-day-old SD rats once a day. At 50 days of age, all rats in the model group and drug groups also received a single ip injection of 60 mg/kg MNU. Rats in group 1 received ip injection of physiological saline. All rats were killed at different times after MNU or physiological saline treatment. The apoptotic index of photoreceptor cells was calculated by TUNEL labeling; retinal damage was evaluated based on retinal thickness and the expression of NF-κB family members was detected by Western blot.
Results:
TMP injections, in a dose-dependent manner, suppressed photoreceptor cell apoptosis and decreased its loss in the peripheral retina. As compared with the MNU-treated group, TMP injection at a dose of 160 mg/kg also time-dependently upregulated the NF-κB/p65 protein level in the nucleus and downregulated the IκBα protein level in the cytoplasm. However, no protective effect of TMP injection on MNU-induced central retinal damage was found.
Conclusion:
TMP injection partially protects against MNU-induced retinal damage by upregulating the nuclear translocation of p65 to inhibit photoreceptor cells apoptosis.
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References
Abler AS, Chang CJ, Ful J, Tso MO, Lam TT . Photic injury triggers apoptosis of photoreceptor cells. Res Commun Mol Pathol Pharmacol 1996; 92: 177–89.
van-Soest S, Westerveld A, de-Jong PT, Bleeker-Wagemakers EM, Bergen AA . Retinitis pigmentosa: defined from a molecular point of view. Surv Ophthalmol 1999; 43: 321–34.
Krishnamoorthy RR, Crawford MJ, Chaturvedi MM, Jain SK, Aggarwal BB, Al-Ubaidi MR, et al. Photo-oxidative stress downmodulates the activity of nuclear factor-kappaB via involvement of caspase-1, leading to apoptosis of photoreceptor cells. J Biol Chem 1999; 274: 3734–43.
Crawford MJ, Krishnamoorthy RR, Rudick VL, Collier RJ, Kapin M, Aggarwal BB, et al. Bcl-2 overexpression protects Photooxidative stress-induced apoptosis of photoreceptor cells via NFkappa B preservation. Biochem Biophys Res Commun 2001; 281: 1304–12.
Sen R, Baltimore D . Inducibility of kappa immunoglobulin enhancer-binding protein NF-κB by a posttranslational mechanism. Cell 1986; 47: 921–8.
Legrand-Poels S, Schoonbroodt S, Matroule JY, Piette J . NFkappa B: an important transcription factor in photobiology. J Photochem Photobiol B 1998; 45: 1–8.
Zhou JY, Tang FD, Mao GG, Bian RL . Effect of α-pinene on nuclear translocation of NF-κB in THP-1 cells. Acta Pharmacol Sin 2004; 25: 480–4.
Souabni A, Cobaleda C, Schebesta M, Busslinger M . Pax5 promotes B lymphopoiesis and blocks T cell development by repressing Notch1. Immunity 2002; 17: 781–93.
Bhakar AL, Tannis LL, Zeindler C, Russo MP, Jobin C, Park DS, et al. Constitutive nuclear factor-kappa B activity is required for central neuron survival. J Neurosci 2002; 22: 8466–75.
Yoshizawa K, Nambu H, Yang J, Oishi Y, Senzaki H, Shikata N, et al. Mechanisms of photoreceptor cell apoptosis induced by Nmethyl-N-nitrosourea in Sprague-Dawley rats. Lab Invest 1999; 79: 1359–67.
Yang JN, Lin SC, Chen JM, Zhang Y, Hu SX . Photoreceptor cell apoptosis of rat's retina induced by N-methyl-N-nitrosourea. Chin J Ocul Fundus Dis 2004; 20: 33–6.
Zhao ZX, Guo XR, Li YS . Characteristics of retinitis pigmentosa in indocyanine green angiography. Chin J Ocul Fundus Dis 2001; 17: 26–9.
Li XY, Yang LZ, Kang FY, Zhang SS, Li GB, Huo YM, et al. The effect of ligustrazaine on the microcirculation of rabbit eyes with continuous elevated IOP. Chin J Microcirc 2001; 5: 119–20.
Feng GQ, Liu J, Fu RF, Feng GY, Weng SI . Protective effect of alprostadil combined with ligustrazine and Astragalus membranaceus on myocardial ischemia reperfusion injury in rats. Chin J New Drugs Clin Remedies 2001; 20: 3–6.
He JK, Gu ZL, Fan PS . Inhibitory effects of prostaglandin A1 on apoptosis of rat cardiac microvascular endothelial cells was mediated by NF-κB. Acta Pharmacol Sin 2002; 23: 331–5.
Karin M, Ben-Neriah Y . Phosphorylation meets ubiquitination: the control of NF-κB activity. Annu Rev Immunol 2000; 18: 621–63.
Zhang Z, Wei T, Hou J, Li G, Yu S, Xin W . Tetramethylpyrazine scavenges superoxide anion and decreases nitric oxide production in human polymorphonuclear leukocytes. Life Sci 2003; 72: 2465–72.
Lu YM, Wan FS, Tang SB . Effects of tetramethylpyrazine on expression of Bcl-2 and Fas proteins in myocardial injury induced by catecholamine in rats. Chin J Clin Pharmacol Ther 2004; 9: 197–200.
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Project supported by the National Natural Science Foundation of China, No 30300467.
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Yang, Jn., Chen, Jm., Luo, L. et al. Tetramethylpyrazine protected photoreceptor cells of rats by modulating nuclear translocation of NF-κB. Acta Pharmacol Sin 26, 887–892 (2005). https://doi.org/10.1111/j.1745-7254.2005.00141.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00141.x
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