title: [Autophagy-lysosome pathway in skeletal muscle of diabetic nephropathy rats and the effect of low-protein diet plus α-keto acids on it].
abstract: OBJECTIVE
  To explore the regulation of autophagy-lysosome pathway (ALP) in skeletal muscle of diabetic nephropathy and examine the effect of low protein diet plus α-keto acid on ALP.
  
  
  METHODS
  A total of 45 24-week-old Goto-Kakizaki rats were randomized to receive normal protein (22%) diet (NPD), low-protein (6%) diet (LPD) or low-protein (5%) plus α-keto acids (1%) diet (Keto) (n = 15 each). Wistar control rats had a normal protein diet. The mRNA and protein levels of ALP markers LC3B, Bnip3, Cathepsin L in soleus muscle were evaluated at 48 weeks. Electron microscopy was used to confirm the changes of autophagy.
  
  
  RESULTS
  Compared with CTL group, the mRNA levels of LC3B, Bnip3, Cathepsin L in soleus muscle of rats on NPD were higher, and protein levels of LC3B-I, LC3B-II, Bnip3, Cathepsin L in soleus muscle of rats on NPD also higher than CTL group (0.82 ± 0.33 vs 0.25 ± 0.07, 0.76 ± 0.38 vs 0.20 ± 0.12, 1.25 ± 0.30 vs 0.56 ± 0.19, 1.29 ± 0.40 vs 0.69 ± 0.20). The mRNA levels of LC3B, Bnip3 and Cathepsin L in LPD group were slightly lower, compared with NPD group. However there was no statistical significance. Similarly the protein levels of LC3B-I, LC3B-II, Bnip3 and Cathepsin L in LPD group were slightly lower with no statistical significance. In contrast, the mRNA levels of LC3B, Bnip3 and Cathepsin L were greatly lower in Keto group in comparison with NPD and LPD. And protein levels of LC3B-I, LC3B-II, Bnip3 and Cathepsin L were also greatly lower in Keto group in comparison with NPD and LPD. Additionally, autophagosome or auto-lysosome was found in NPD and LPD groups by electron microscopy.
  
  
  CONCLUSIONS
  ALP is activated in skeletal muscle of diabetic nephropathy rats. And low protein plus α-keto acid decrease the activation of ALP and improve muscle wasting.
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Juan
authors: J
authors: Huang
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China. Email: ywj4169@163.com.
authors: Wei-jie
authors: WJ
authors: Yuan
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Jia-lin
authors: JL
authors: Wang
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Li-jie
authors: LJ
authors: Gu
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Jun
authors: J
authors: Yin
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Ting
authors: T
authors: Dong
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Jin-fang
authors: JF
authors: Bao
authors: Department of Nephrology, Affiliated First People's Hospital, Shanghai Jiaotong University, Shanghai 200080, China.
authors: Zhi-huan
authors: ZH
authors: Tang
mesh_terms: D000818:Animals; D001343:Autophagy; D003928:Diabetic Nephropathies / Q000378:metabolism*; D018753:Diet, Protein-Restricted; D007651:Keto Acids / Q000494:pharmacology*; D008247:Lysosomes / Q000378:metabolism; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism*; D051381:Rats
chemical_list: D007651:Keto Acids