Opposing responses of apoptosis and autophagy to moderate compression in skeletal muscle

Aim: The molecular mechanism that contributes to the pathogenesis of deep pressure ulcer remains to be elucidated. This study tested the hypotheses that: (1) apoptosis and autophagy are activated in compression-induced muscle pathology and (2) apoptotic and autophagic changes precede pathohistologic...

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Published in:	Acta Physiologica Vol. 201; no. 2; pp. 239 - 254
Main Authors:	Teng, B.T, Pei, X.M, Tam, E.W, Benzie, I.F, Siu, P.M
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-02-2011 Wiley-Blackwell
Subjects:	Animals Apoptosis Apoptosis Regulatory Proteins - metabolism Autophagy Beclin-1 bedsore Biological and medical sciences Biomarkers - metabolism caspase Caspases - metabolism deep pressure ulcer DNA Fragmentation Female Forkhead Box Protein O3 Forkhead Transcription Factors - metabolism Fundamental and applied biological sciences. Psychology In Situ Nick-End Labeling Microtubule-Associated Proteins - metabolism Muscle, Skeletal - enzymology Muscle, Skeletal - pathology Pressure Ulcer - enzymology Pressure Ulcer - etiology Pressure Ulcer - pathology programmed cell death Proto-Oncogene Proteins c-akt - metabolism Rats Rats, Sprague-Dawley Time Factors Vertebrates: anatomy and physiology, studies on body, several organs or systems Skin disease Compression bedsore deep pressure ulcer Enzyme Cysteine endopeptidases Caspase Pressure sore Striated muscle Peptidases Vertebrata Mammalia Hydrolases programmed cell death Apoptosis
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Summary:	Aim: The molecular mechanism that contributes to the pathogenesis of deep pressure ulcer remains to be elucidated. This study tested the hypotheses that: (1) apoptosis and autophagy are activated in compression-induced muscle pathology and (2) apoptotic and autophagic changes precede pathohistological changes in skeletal muscle in response to prolonged moderate compression. Methods: Adult Sprague-Dawley rats were subjected to an experimental model of pressure-induced deep tissue injury. Static pressure of 100 mmHg was applied to an area of 1.5 cm² over the mid-tibialis region of right limb of rats for one single session of 6-h compression (1D) or two sessions of 6-h compression over two consecutive days with rats sacrificed one day (2D) or immediately after (2D-IM) the compression. The left uncompressed limb served as the intra-animal control. Muscle tissues underneath compression region were collected for analysis. Results: Our histological analysis indicated that pathohistological characteristics including rounding contour of myofibres and massive nuclei accumulation were apparently demonstrated in muscles of 2D and 2D-IM. In contrast, these pathohistological changes were generally not found in muscle following 1D. Apoptotic DNA fragmentation, terminal dUTP nick-end labelling index and caspase-3 protease activity were significantly elevated in compressed muscles of all groups. Caspase-9 enzymatic activity was found to be significantly increased in compressed muscles of 2D and 2D-IM whereas increase in caspase-8 activity was exclusively found in compressed muscle of 1D. According to our immunoblot analysis, FoxO3 was significantly reduced in compressed muscles of all groups whereas Beclin-1 was decreased only in 2D. LC3-I was significantly reduced in compressed muscles of all groups while LC3-II was decreased in 2D and 1D. No significant differences were found in the protein abundance of Akt and phospho-Akt in muscles among all groups. Conclusion: These data demonstrate the opposing responses of apoptosis and autophagy to moderate compression in muscle. Moreover, our findings suggest that cellular changes in apoptosis and autophagy have already taken place in the very early stage in which apparent histopathology has yet to develop in the process of compression-induced muscle pathology.
Bibliography:	http://dx.doi.org/10.1111/j.1748-1716.2010.02173.x ArticleID:APHA2173 istex:16041809A1EAC2677FAB64CF20A9154E9278EF95 ark:/67375/WNG-77NJKWQ6-V ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1748-1708 1748-1716
DOI:	10.1111/j.1748-1716.2010.02173.x