EFFECT OF LIGUSTRAZINE ON EXPRESSIONS OF FoXO3a, MAFbx, AND MuRF1 IN DENERVATED SKELETALMUSCLE ATROPHY RATS/_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WANG Hongbing , LIANG Bingsheng , PENG Chunhui , WANG Pengfei.

Department of Orthopaedics,Second Affiliated Hospital of Shanxi Medical University, Taiyuan Shanxi, 030001, P.R.China.;

Corresponding author：

Keywords：

FoXO3a, MAFbx ,MuRF1, Ligustrazine, Denervation Muscle atrophy ,Rat

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Objective To investigate the effect of Ligustrazine on the expressions of FoXO3a, MAFbx, and MuRF1 in
denervated skeletal muscle atrophy rats. Methods Fifty-four 8-week-old female Sprague Dawley rats were randomly divided
into 3 groups: normal control group (group A, n=6), denervated control group (group B, n=24), and Ligustrazine intervention
group (group C, n=24). After the denervated gastrocnemius models were established in the rats of groups B and C, sal ine and
Ligustrazine [80 mg/(kg·d)] were given every day by intraperitoneal injection, respectively. However, no treatment was done
in group A. At 2, 7, 14, and 28 days after denervation, the wet weight of gastrocnemius was measured to calculate the ratio of
wet weight. The mRNA and protein expression levels of FoXO3a, MAFbx, and MuRF1 were detected by RT-PCR and Western
blot. Results The ratio of gastrocnemius wet weight decreased with time after denervation in groups B and C, showing
significant differences when compared with that of group A (P lt; 0.05), and group C were significantly higher than that of group
B at 7, 14, and 28 days (P lt; 0.05). The mRNA and protein expressions of FoXO3a, MAFbx, and MuRF1 in groups B and C
were significantly higher than those in group C at 7, 14, and 28 days (P lt; 0.05), and group C was significantly lower than group
B (P lt; 0.05). Conclusion Ligustrazine may postpone denervated skeletal muscle atrophy by reducing mRNA and protein
expressions of FoXO3a, MAFbx, and MuRF1.

Citation： WANG Hongbing,LIANG Bingsheng,PENG Chunhui,WANG Pengfei.. EFFECT OF LIGUSTRAZINE ON EXPRESSIONS OF FoXO3a, MAFbx, AND MuRF1 IN DENERVATED SKELETALMUSCLE ATROPHY RATS/. Chinese Journal of Reparative and Reconstructive Surgery, 2012, 26(5): 597-600. doi: Copy

1.	Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev, 2002, 82(2): 373-428.
2.	Zhao J, Brault JJ, Schild A, et al. Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy, 2008, 4(3): 378-380.
3.	Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy, 2008, 4(4): 524-526.
4.	刘安唐, 江华. MAFbx/Atrogin-1和MuRF1在大鼠肌肉游离移植模型中的表达和意义. 上海: 第二军医大学, 2007.
5.	Jones A, Hwang DJ, Narayanan R, et al. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology, 2010, 151(8): 3706-3719.
6.	Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal Muscle Atrophy. Science, 2001, 294(5547): 1704-1708.
7.	Chen YW, Gregory CM, Scarborough MT, et al. Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics, 2007, 31(3): 510-520.
8.	Dehoux M, Van Beneden R, Pasko N, et al. Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology, 2004, 145(11): 4806-4812.
9.	Dehoux MJ, van Beneden RP, Fernández-Celemín L, et al. Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett, 2003, 544(1-3): 214-217.
10.	Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol, 2007, 292(1): C188-C199.
11.	Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004, 117(3): 399-412.
12.	Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol, 2010, 298(1): C38-C45.
13.	Sandri M, Lin J, Handschin C, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A, 2006, 103(44): 16260-16265.
14.	Asensio-Pinilla E, Udina E, Jaramillo J, et al. Electrical stimulation combined with exercise increase axonal regeneration after peripheral nerve injury, Exp Neurol, 2009, 219(1): 258-265.
15.	Dong F, Hua Y, Zhao P, et al. Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J Nutr Biochem, 2009, 20(12): 992-999.
16.	Jin B, Li YP. Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. J Cell Biochem, 2007, 100(4): 960-969.
17.	秦雯. 当归和川芎对尾部悬吊大鼠比目鱼肌的影响及其机制研究. 西安: 西北大学, 2008.
18.	高云芳, 樊小力, 何志仙, 等. 川芎嗪和黄芪对尾部悬吊大鼠比目鱼肌肌球蛋白ATP酶活性及肌萎缩的影响. 航天医学与医学工程, 2005, 18(4): 262-266.
19.	曹晋, 高云芳, 刘坤. 川芎及两种主要药效成分对废用性肌萎缩的影响. 中国应用生理学杂志, 2010, 26(1): 109-113.
20.	de Palma L, Marinelli M, Pavan M, et al. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine, 2008, 75(1): 53-57.
21.	Yoshida T, Semprun-Prieto L, Sukhanov S, et al. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol, 2010, 298(5): H1565-H1570.
22.	Doucet M, Russell AP, Léger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 176(3): 261-269.
23.	Mcelhinny AS, Kakinuma K, Sorimachi H, et al. Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and May have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol, 2002, 157(1): 125-136.
24.	Witt CC, Witt SH, Lerche S, et al. Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J, 2008, 27(2): 350-360.
25.	Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A, 2001, 98(25): 14440-14445.
26.	Poylin V, Fareed MU, O’Neal P, et al. The NF-κB inhibitor curcumin blocks Sepsis-Induced muscle proteolysis. Mediators Inflamm, 2008, 317851.
27.	Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 2004, 117(4): 421-426.
28.	Sáinz N, Rodríguez A, Catalán V, et al. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One, 2009, 4(9): e6808.
29.	曹晋. 川芎及其主要成分和达乌尔黄鼠冬眠期抗废用性肌萎缩的机制研究. 西安: 西北大学, 2009.
30.	李光月, 高云芳. 川芎嗪抗废用性肌萎缩药效作用与作用机制初步研究. 西安: 西北大学, 2011.

1. Glickman MH, Ciechanover A. The ubiquitin-proteasome proteolytic pathway: destruction for the sake of construction. Physiol Rev, 2002, 82(2): 373-428.
2. Zhao J, Brault JJ, Schild A, et al. Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy, 2008, 4(3): 378-380.
3. Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy, 2008, 4(4): 524-526.
4. 刘安唐, 江华. MAFbx/Atrogin-1和MuRF1在大鼠肌肉游离移植模型中的表达和意义. 上海: 第二军医大学, 2007.
5. Jones A, Hwang DJ, Narayanan R, et al. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy. Endocrinology, 2010, 151(8): 3706-3719.
6. Bodine SC, Latres E, Baumhueter S, et al. Identification of ubiquitin ligases required for skeletal Muscle Atrophy. Science, 2001, 294(5547): 1704-1708.
7. Chen YW, Gregory CM, Scarborough MT, et al. Transcriptional pathways associated with skeletal muscle disuse atrophy in humans. Physiol Genomics, 2007, 31(3): 510-520.
8. Dehoux M, Van Beneden R, Pasko N, et al. Role of the insulin-like growth factor I decline in the induction of atrogin-1/MAFbx during fasting and diabetes. Endocrinology, 2004, 145(11): 4806-4812.
9. Dehoux MJ, van Beneden RP, Fernández-Celemín L, et al. Induction of MafBx and Murf ubiquitin ligase mRNAs in rat skeletal muscle after LPS injection. FEBS Lett, 2003, 544(1-3): 214-217.
10. Allen DL, Unterman TG. Regulation of myostatin expression and myoblast differentiation by FoxO and SMAD transcription factors. Am J Physiol Cell Physiol, 2007, 292(1): C188-C199.
11. Sandri M, Sandri C, Gilbert A, et al. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell, 2004, 117(3): 399-412.
12. Senf SM, Dodd SL, Judge AR. FOXO signaling is required for disuse muscle atrophy and is directly regulated by Hsp70. Am J Physiol Cell Physiol, 2010, 298(1): C38-C45.
13. Sandri M, Lin J, Handschin C, et al. PGC-1alpha protects skeletal muscle from atrophy by suppressing FoxO3 action and atrophy-specific gene transcription. Proc Natl Acad Sci U S A, 2006, 103(44): 16260-16265.
14. Asensio-Pinilla E, Udina E, Jaramillo J, et al. Electrical stimulation combined with exercise increase axonal regeneration after peripheral nerve injury, Exp Neurol, 2009, 219(1): 258-265.
15. Dong F, Hua Y, Zhao P, et al. Chromium supplement inhibits skeletal muscle atrophy in hindlimb-suspended mice. J Nutr Biochem, 2009, 20(12): 992-999.
16. Jin B, Li YP. Curcumin prevents lipopolysaccharide-induced atrogin-1/MAFbx upregulation and muscle mass loss. J Cell Biochem, 2007, 100(4): 960-969.
17. 秦雯. 当归和川芎对尾部悬吊大鼠比目鱼肌的影响及其机制研究. 西安: 西北大学, 2008.
18. 高云芳, 樊小力, 何志仙, 等. 川芎嗪和黄芪对尾部悬吊大鼠比目鱼肌肌球蛋白ATP酶活性及肌萎缩的影响. 航天医学与医学工程, 2005, 18(4): 262-266.
19. 曹晋, 高云芳, 刘坤. 川芎及两种主要药效成分对废用性肌萎缩的影响. 中国应用生理学杂志, 2010, 26(1): 109-113.
20. de Palma L, Marinelli M, Pavan M, et al. Ubiquitin ligases MuRF1 and MAFbx in human skeletal muscle atrophy. Joint Bone Spine, 2008, 75(1): 53-57.
21. Yoshida T, Semprun-Prieto L, Sukhanov S, et al. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt- and Foxo-dependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol, 2010, 298(5): H1565-H1570.
22. Doucet M, Russell AP, Léger B, et al. Muscle atrophy and hypertrophy signaling in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med, 2007, 176(3): 261-269.
23. Mcelhinny AS, Kakinuma K, Sorimachi H, et al. Muscle-specific RING finger-1 interacts with titin to regulate sarcomeric M-line and thick filament structure and May have nuclear functions via its interaction with glucocorticoid modulatory element binding protein-1. J Cell Biol, 2002, 157(1): 125-136.
24. Witt CC, Witt SH, Lerche S, et al. Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J, 2008, 27(2): 350-360.
25. Gomes MD, Lecker SH, Jagoe RT, et al. Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy. Proc Natl Acad Sci U S A, 2001, 98(25): 14440-14445.
26. Poylin V, Fareed MU, O’Neal P, et al. The NF-κB inhibitor curcumin blocks Sepsis-Induced muscle proteolysis. Mediators Inflamm, 2008, 317851.
27. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell, 2004, 117(4): 421-426.
28. Sáinz N, Rodríguez A, Catalán V, et al. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice. PLoS One, 2009, 4(9): e6808.
29. 曹晋. 川芎及其主要成分和达乌尔黄鼠冬眠期抗废用性肌萎缩的机制研究. 西安: 西北大学, 2009.
30. 李光月, 高云芳. 川芎嗪抗废用性肌萎缩药效作用与作用机制初步研究. 西安: 西北大学, 2011.

Chinese Journal of Reparative and Reconstructive Surgery

EFFECT OF LIGUSTRAZINE ON EXPRESSIONS OF FoXO3a, MAFbx, AND MuRF1 IN DENERVATED SKELETALMUSCLE ATROPHY RATS/

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