Effect of Modified Wuzi Yanzong Pill(五子衍宗丸) on Tip60-Mediated Apoptosis in Testis of Male Rats after Microwave Radiation
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摘要
Objective: To investigate the effect of a modi?ed Wuzi Yanzong Pill(五子衍宗丸, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. Methods: Forty-?ve male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modi?ed of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin(HE) staining. Tat-interactive protein, 60 kD(Tip60) and p53 expressions were determined by Western blotting. Results: The apoptosis index(AI) in the radiation group was higher than that of the WZYZP group and control group on day 1(D1), day 7(D7) day 14(D14) after radiation(P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group(P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14(P<0.05). Conclusion: A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.
Objective: To investigate the effect of a modi?ed Wuzi Yanzong Pill(五子衍宗丸, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. Methods: Forty-?ve male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modi?ed of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin(HE) staining. Tat-interactive protein, 60 kD(Tip60) and p53 expressions were determined by Western blotting. Results: The apoptosis index(AI) in the radiation group was higher than that of the WZYZP group and control group on day 1(D1), day 7(D7) day 14(D14) after radiation(P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group(P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14(P<0.05). Conclusion: A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.
Objective: To investigate the effect of a modi?ed Wuzi Yanzong Pill(五子衍宗丸, WZYZP) on the male rats' testis after microwave radiation, as well as its potential mechanism. Methods: Forty-?ve male rats were randomly assigned to three groups: the control group, the radiation group, and the WZYZP group. The rats in the radiation group and WZYZP group were exposed to microwave radiation for 15 min once, while the rats in the control group were not exposed to any radiation. The rats in the WZYZP group were given a modi?ed of WZYZP by gavage daily for 7 days. Apoptosis in the testis was evaluated using terminal-deoxynucleoitidyl transferase mediated nick end labeling(TUNEL) assay. Histopathological alterations of the testis were observed by haematoxylin-eosin(HE) staining. Tat-interactive protein, 60 kD(Tip60) and p53 expressions were determined by Western blotting. Results: The apoptosis index(AI) in the radiation group was higher than that of the WZYZP group and control group on day 1(D1), day 7(D7) day 14(D14) after radiation(P<0.05). The seminiferous tubules were of normal morphology in the control group. In the radiation group, the partial seminiferous tubules were collapsed, basement membranes of the seminiferous epithelia became detached. WZYZP could restore the morphological changes. There was no expression of Tip60 among the three groups on D7 and D14. The expression of p53 was higher in the radiation group than in the control group(P<0.05). WZYZP could down-regulate the rising p53 induced by radiation on D7 and D14(P<0.05). Conclusion: A modified WZYZP may affect germ cells, and its protective effects may partly result from its ability to intervene in Tip60 mediated apoptosis.
引文
1.Kesari KK,Kumar S,Behari J.Effects of radiofrequency electromagnetic wave exposure from cellular phones on the reproductive pattern in male Wistar rats.Appl Biochem Biotech 2011;164:546-559.
2.Shahin S,Mishra V,Singh SP,Chaturvedi CM.2.45-GHz microwave irradiation adversely affects reproductive function in male mouse,Mus musculus by inducing oxidative and nitrosative stress.Free Radical Res 2014;48:511-525.
3.Sepehrimanesh M,Saeb M,Nazifi S,Kazemipour N,Jelodar G,Saeb S.Impact of 900 MHz electromagnetic field exposure on main male reproductive hormone levels:a Rattus norvegicus model.Int J Biometeorol 2014;58:1657-1663.
4.Meena R,Kumari K,Kumar J,Rajamani P,Verma HN,Kesari KK.Therapeutic approaches of melatonin in microwave radiations-induced oxidative stress-mediated toxicity on male fertility pattern of Wistar rats.Electromagn Biol Med 2014;33:81-91.
5.Odaci E,Ozyilmaz C.Exposure to a 900 MHz electromagnetic field for 1 hour a day over 30 days does change the histopathology and biochemistry of the rat testis.Int J Radiat Biol 2015;91:547-554.
6.Shokri S,Soltani A,Kazemi M,Sardari D,Mofrad FB.Effects of Wi-Fi(2.45 GHz)exposure on apoptosis,sperm parameters and testicular histomorphometry in rats:a time course study.Cell J 2015;17:322-331.
7.Bin-Meferij MM,El-Kott AF.The radioprotective effects of Moringa oleifera against mobile phone electromagnetic radiation-induced infertility in rats.Int J Clin Exp Med2015;8:12487-12497.
8.Xu SQ,Hu HX,Luo SB,Wei LZ,Dong J,Ding HH,et al.Effect of microwave radiation on sex hormone and spermatic quality of radar operators.Med J Beijing Mil Reg(Chin)2013;25:41-43.
9.Hu HX,Ding HH,Luo SB,Xu SQ,Gao YJ,Xie YL,et al.Influence of microwave radiation on the sperm apoptosis of radar operators.Med J Beijing Mil Reg(Chin)2014;26:94-96.
10.Thompson CB.Apoptosis in the pathogenesis and treatment of disease.Science 1995;267:1456-1462.
11.Aitken RJ,De Iuliis GN.Origins and consequences of DNA damage in male germ cells.Reprod Biomed Online2007;14:727-733.
12.Bird AW,Yu DY,Pray-Grant MG,Qiu Q,Harmon KE,Megee PC,et al.Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair.Nature2002;419:411-415.
13.Sun Y,Jiang X,Chen S,Fernandes N,Price BD.Arole for the Tip60 histone acetyltransferase in the acetylation and activation of ATM.P Natl Acad Sci USA2005;102:13182-13187.
14.Ikura T,Ogryzko VV,Grigoriev M,Groisman R,Wang J,Horikoshi M,et al.Involvement of the Tip60 histone acetylase complex in DNA repair and apoptosis.Cell2000;102:463-473.
15.Wu Q,Hu H,Lan J,Emenari C,Wang Z,Chang K-S,et al.PML3 orchestrates the nuclear dynamics and function of Tip60.J Biol Chem 2009;284:8747-8759.
16.Kranz D,Dohmesen C,Dobbelstein M.BRCA1 and Tip60determine the cellular response to ultraviolet irradiation through distinct pathways.J Cell Biol 2008;182:197-213.
17.Levine AJ.p53,the cellular gatekeeper for growth and division.Cell 1997;88:323-331.
18.Tang Y,Luo J,Zhang W,Gu W.Tip60-dependent acetylation of p53 modulates the decision between cellcycle arrest and apoptosis.Mol Cell 2006;24:827-839.
19.Sykes SM,Mellert HS,Holbert MA,Li K,Marmorstein R,Lane WS,et al.Acetylation of the p53 DNA-binding domain regulates apoptosis induction.Mol Cell 2006;24:841-851.
20.Hu HX,Luo SB,Sun J,Wei LZ,Dong J,Liu HY,et al.Influence of Yiqi Yangyin Shengjing Fang on reproduction in rats after microwave radiation.J Beijing Univ Tradit Chin Med(Chin)2013;36:250-253.
21.Chen H,Wang S,Peng R,Gao Y,Wang L,Zhao L,et al.Long-term microwave radiation affects male reproduction in rats.National J Androl 2011;17:214-218.
22.Zhao LW,Zhong XH,Sun YM,Yang SY,Shen N,Zhang YZ,et al.Prevention of Inonotus obliquus polysaccharides for high power microwave radiation induced testicular injury in rats:an experimental research.Chin J Integr Tradit West Med(Chin)2014;34:864-868.
23.Tas M,Dasdag S,Akdag MZ,Cirit U,Yegin K,Seker U,et al.Long-term effects of 900 MHz radiofrequency radiation emitted from mobile phone on testicular tissue and epididymal semen quality.Electromagn Biol Med2014;33:216-222.
24.Bi HZ.Theory of fire pathomechanism of electromagnetic radiation damage.Chin J Basic Med Tradit Chin Med(Chin)2011;17:576-578
25.Legube G,Linares LK,Lemercier C,Scheffner M,Khochbin S,Trouche D.Tip60 is targeted to proteasome-mediated degradation by MDM2 and accumulates after UV irradiation.EMBO J 2002;21:1704-1712.
2.Shahin S,Mishra V,Singh SP,Chaturvedi CM.2.45-GHz microwave irradiation adversely affects reproductive function in male mouse,Mus musculus by inducing oxidative and nitrosative stress.Free Radical Res 2014;48:511-525.
3.Sepehrimanesh M,Saeb M,Nazifi S,Kazemipour N,Jelodar G,Saeb S.Impact of 900 MHz electromagnetic field exposure on main male reproductive hormone levels:a Rattus norvegicus model.Int J Biometeorol 2014;58:1657-1663.
4.Meena R,Kumari K,Kumar J,Rajamani P,Verma HN,Kesari KK.Therapeutic approaches of melatonin in microwave radiations-induced oxidative stress-mediated toxicity on male fertility pattern of Wistar rats.Electromagn Biol Med 2014;33:81-91.
5.Odaci E,Ozyilmaz C.Exposure to a 900 MHz electromagnetic field for 1 hour a day over 30 days does change the histopathology and biochemistry of the rat testis.Int J Radiat Biol 2015;91:547-554.
6.Shokri S,Soltani A,Kazemi M,Sardari D,Mofrad FB.Effects of Wi-Fi(2.45 GHz)exposure on apoptosis,sperm parameters and testicular histomorphometry in rats:a time course study.Cell J 2015;17:322-331.
7.Bin-Meferij MM,El-Kott AF.The radioprotective effects of Moringa oleifera against mobile phone electromagnetic radiation-induced infertility in rats.Int J Clin Exp Med2015;8:12487-12497.
8.Xu SQ,Hu HX,Luo SB,Wei LZ,Dong J,Ding HH,et al.Effect of microwave radiation on sex hormone and spermatic quality of radar operators.Med J Beijing Mil Reg(Chin)2013;25:41-43.
9.Hu HX,Ding HH,Luo SB,Xu SQ,Gao YJ,Xie YL,et al.Influence of microwave radiation on the sperm apoptosis of radar operators.Med J Beijing Mil Reg(Chin)2014;26:94-96.
10.Thompson CB.Apoptosis in the pathogenesis and treatment of disease.Science 1995;267:1456-1462.
11.Aitken RJ,De Iuliis GN.Origins and consequences of DNA damage in male germ cells.Reprod Biomed Online2007;14:727-733.
12.Bird AW,Yu DY,Pray-Grant MG,Qiu Q,Harmon KE,Megee PC,et al.Acetylation of histone H4 by Esa1 is required for DNA double-strand break repair.Nature2002;419:411-415.
13.Sun Y,Jiang X,Chen S,Fernandes N,Price BD.Arole for the Tip60 histone acetyltransferase in the acetylation and activation of ATM.P Natl Acad Sci USA2005;102:13182-13187.
14.Ikura T,Ogryzko VV,Grigoriev M,Groisman R,Wang J,Horikoshi M,et al.Involvement of the Tip60 histone acetylase complex in DNA repair and apoptosis.Cell2000;102:463-473.
15.Wu Q,Hu H,Lan J,Emenari C,Wang Z,Chang K-S,et al.PML3 orchestrates the nuclear dynamics and function of Tip60.J Biol Chem 2009;284:8747-8759.
16.Kranz D,Dohmesen C,Dobbelstein M.BRCA1 and Tip60determine the cellular response to ultraviolet irradiation through distinct pathways.J Cell Biol 2008;182:197-213.
17.Levine AJ.p53,the cellular gatekeeper for growth and division.Cell 1997;88:323-331.
18.Tang Y,Luo J,Zhang W,Gu W.Tip60-dependent acetylation of p53 modulates the decision between cellcycle arrest and apoptosis.Mol Cell 2006;24:827-839.
19.Sykes SM,Mellert HS,Holbert MA,Li K,Marmorstein R,Lane WS,et al.Acetylation of the p53 DNA-binding domain regulates apoptosis induction.Mol Cell 2006;24:841-851.
20.Hu HX,Luo SB,Sun J,Wei LZ,Dong J,Liu HY,et al.Influence of Yiqi Yangyin Shengjing Fang on reproduction in rats after microwave radiation.J Beijing Univ Tradit Chin Med(Chin)2013;36:250-253.
21.Chen H,Wang S,Peng R,Gao Y,Wang L,Zhao L,et al.Long-term microwave radiation affects male reproduction in rats.National J Androl 2011;17:214-218.
22.Zhao LW,Zhong XH,Sun YM,Yang SY,Shen N,Zhang YZ,et al.Prevention of Inonotus obliquus polysaccharides for high power microwave radiation induced testicular injury in rats:an experimental research.Chin J Integr Tradit West Med(Chin)2014;34:864-868.
23.Tas M,Dasdag S,Akdag MZ,Cirit U,Yegin K,Seker U,et al.Long-term effects of 900 MHz radiofrequency radiation emitted from mobile phone on testicular tissue and epididymal semen quality.Electromagn Biol Med2014;33:216-222.
24.Bi HZ.Theory of fire pathomechanism of electromagnetic radiation damage.Chin J Basic Med Tradit Chin Med(Chin)2011;17:576-578
25.Legube G,Linares LK,Lemercier C,Scheffner M,Khochbin S,Trouche D.Tip60 is targeted to proteasome-mediated degradation by MDM2 and accumulates after UV irradiation.EMBO J 2002;21:1704-1712.