Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Zhang, J; Li, Y; Li, G; Ma, X; Wang, H; Goswami, N; Hinghofer-Szalkay, H; Chang, H; Gao, Y.
Identification of the optimal dose and calpain system regulation of tetramethylpyrazine on the prevention of skeletal muscle atrophy in hindlimb unloading rats.
Biomed Pharmacother. 2017; 96(10):513-523
Doi: 10.1016/j.biopha.2017.10.012
Web of Science
PubMed
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FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Goswami Nandu
- Hinghofer-Szalkay Helmut
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- Abstract:
- Previous studies in our lab have shown that tetramethylpyrazine (TMP) could effectively attenuate disuse induced muscle atrophy. In order to screening out the optimal dose of tetramethylpyrazine (TMP) for protection against disuse induced muscle atrophy in hindlimb unloading (HLU) rats, in this study, we compared effects of 4 TMP doses on muscle wet weight (MWW), the ratios of muscle wet weight/body weight (MWW/BW) and muscle wet weight/dry weight (MWW/DW), fiber type composition, as well as cross-sectional area (CSA) in soleus (SOL) muscle. Consequently, we quantified optimal dose effects on both functional properties and protein expression (calpain-1, calpain-2, calpastatin and MuRF1) in SOL and extensor digitorum longus (EDL) muscles. Data indicated that the protective potential of TMP was dose-dependent: 60mg/kg TMP was most effective in terms of atrophy prevention. This dose reduced SOL MWW, MWW/BW and CSA muscle loss by 60, 60 and 54% (P<0.001), respectively. HLU-induced slow-to-fast fiber transition was reduced by 17% (P<0.01). 60mg/kg TMP also significantly lessened the decrease of contractile force, the increase of shorting velocity and fatigability induced by HLU. Besides, it also attenuated expressions of calpain-1 (SOL -8.6%, P<0.05; EDL -10.9%, P<0.05), calpain-2 (SOL -60%, P<0.001; EDL -32%, P<0.01) and MuRF1 expression (SOL -21%, P<0.001; EDL -10%, P<0.01), promoted the expression of calpastatin by 18% (P<0.05) in SOL muscle. Taken together, present study demonstrated that 60mg/kg body weight was the optimal dose of TMP against disuse induced muscle atrophy which effectively protected muscle function by inhibiting calpain-1, calpain-2 and MuRF1 expression, promoted calpastatin expression, especially in slow-twitch muscle. Copyright © 2017 Elsevier Masson SAS. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Calpain - physiology
- Dose-Response Relationship, Drug -
- Female -
- Hindlimb Suspension - methods
- Hindlimb Suspension - physiology
- Muscle Contraction - drug effects
- Muscle Contraction - physiology
- Muscle, Skeletal - drug effects
- Muscle, Skeletal - physiology
- Muscular Atrophy - drug therapy
- Muscular Atrophy - prevention & control
- Pyrazines - administration & dosage
- Rats -
- Rats, Sprague-Dawley -
- Vasodilator Agents - administration & dosage
- Find related publications in this database (Keywords)
- Tetramethylpyrazine
- Disuse atrophy
- Muscle functional properties
- Calpains