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Decreased anti‐apoptotic ARC and XIAP as well as elevated pro‐apoptotic Smac and procaspase‐8 protein in soleus muscle of hypertensive rats
Author(s) -
Quadrilatero Joe,
Rush James W.E.
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1238.12
Subject(s) - xiap , apoptosis , skeletal muscle , endocrinology , medicine , soleus muscle , western blot , inhibitor of apoptosis , caspase , caspase 12 , chemistry , myocyte , biochemistry , gene , programmed cell death
Elevated skeletal muscle apoptosis plays a significant role in age‐ and disease‐related muscle wasting and dysfunction. Recently, we have demonstrated increased apoptosis in skeletal muscle of hypertensive rats. In this report we extend our previous findings by evaluating several pro‐ and anti‐apoptotic proteins involved in caspase‐mediated apoptotic signaling in skeletal muscle of normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR). Protein levels of apoptosis repressor with caspase recruitment domain (ARC) and X‐linked inhibitor of apoptosis protein (XIAP) were significantly lower by 59% (p<0.001) and 44% (p<0.05), respectively, in soleus muscle of SHR compared to WKY rats. In contrast, protein levels of the IAP inhibitor, second mitochondria‐derived activator of caspases (Smac), and pro‐apoptotic procaspase‐8 were elevated by 33% (p<0.005) and 32% (p<0.005), respectively, in hypertensive rats. Interestingly, western blot analysis revealed that ARC protein migrated at 30kDa in WKY and 32kDa in SHR soleus muscle; possibly suggesting a posttranslational modification in hypertensive rats. This data confirms our previous findings and suggests that alterations in proteins involved in caspase‐mediated signaling may be responsible for elevated apoptosis in skeletal muscle during hypertension. Research supported by the Heart & Stroke Foundation of Ontario and NSERC Canada.