In the current study adiponectin receptors expressions

In the current study, adiponectin receptors expressions were detected in both cell lines. AdipoR2 showed equal expression levels, whereas AdipoR1 possessed different expression levels in both cell lines. There was a significant increase in the AdipoR1 mRNA levels in cell lines according to AdipoR2 mRNA levels. AdipoR1 levels were found significantly higher in Meg-01 cells than those in K562 cells. This difference in AdipoR1 levels between cell lines could be due to their different origins and similar result was reported in a previous study, stating the different expression levels of AdipoR1, and unaltered AdipoR2 expression in PBMC subsets [35]. While in almost all healthy individuals AdipoR2 was found to be expressed in high levels, its level in newly diagnosed and in imatinib treated CML patients was low. On the contrary, AdipoR1 expression was significantly increased the CML patients, and this increase was similar in newly diagnosed and in imatinib treated CML patients. According to our results, the increase in AdipoR1 expression and the opposite decrease in AdipoR2 expression are related to CML pathogenesis. This result leads to the possibility of different functions of the two adiponectin receptors in CML development. In fact, AdipoR1 and AdipoR2 were reported to mediate most effects of adiponectin, such as stimulation of glucose transport [36]. However another report showed that AdipoR1-knockout mice had impaired glucose tolerance; on the other hand, glucose intolerance was not observed in AdipoR2-knockout mice [37] which suggest that AdipoR1 plays a more important role in glucose metabolism than AdipoR2. This supporting evidence together with the high dependence of cancer cells to glucose metabolism can explain why AdipoR1 expression is high in CML patients. The lower expression of AdipoR2 in CML patients remains to be determined.
Conclusion
Conflict of interest statement
Acknowledgements This work was supported by Gulhane Military Medical Academy Research Fund.
Introduction In addition to being a major structural and mechanical organ, skeletal muscle is the primary protein reservoir in vertebrates. Skeletal muscle is highly plastic in nature in relation to various physical and chemical stimuli and can convert proteins into free dpp4 for hepatic gluconeogenesis and energy production during starvation and pathological conditions (Gomes et al., 2001). Excessive protein breakdown and lack of new protein synthesis in skeletal muscle can result in muscle atrophy. Muscle atrophy is characterized by loss of muscle mass leading to partial or complete loss of its function. Major diseases like AIDS, cancer, chronic obstructive pulmonary disorder, diabetes, renal failure, cardiac failure and septicemia lead to muscle atrophy (Sacheck et al., 2007). Muscle atrophy also may occur as a debilitating response to muscle disuse, malnutrition, fasting, steroid administration and denervation due to loss of motor neurons, and it is a consequence of biological aging as well (Bonaldo and Sandri, 2013). Skeletal muscle mass depends on number of muscle fibers, their type, size and balance between myofibrillar protein synthesis and degradation (Siriett et al., 2007). The two important proteolytic systems controlling myofibrillar protein turnover are ubiquitin proteasome machinery and the autophagy-lysosome machinery (Sacheck et al., 2007, Bonaldo and Sandri, 2013). Proteasome machinery inhibitors like bortezomib (Velcade) and MG132 have been shown to effectively block myofibrillar proteolysis in vitro as well as in muscle atrophy induced by denervation in vivo (Caron et al., 2011). A comparative cDNA microarray analysis of mRNA samples from muscles of different atrophy models including fasting, cancer cachexia, streptozotocin induced diabetes mellitus, chronic renal failure and denervation revealed that a common subset of genes were up or down-regulated in all the atrophy models (Gomes et al., 2001, Sacheck et al., 2007, Lecker et al., 2004, Jagoe et al., 2002, Bodine et al., 2001a, Bodine et al., 2001b). These common set of genes which were coordinately regulated in atrophy were named as “atrogenes” (Sacheck et al., 2007, Sandri et al., 2004, Sandri et al., 2006). The most highly upregulated atrogenes in muscle atrophy are the two “muscle-specific” E3 ubiquitin ligases Atrogin-1 (also called Muscle Atrophy F-box protein or MAFbx) and Muscle-specific Ring Finger protein1 (MuRF1). While MuRF1 is involved in degradation of myocyte structural proteins such as myosin heavy chain 1,4,8, MyBPc, alpha actin, filamin c etc (Cohen et al., 2009), atrogin-1 majorly regulates the stability of myocyte functional components such as the key myogenic transcription factor MyoD (Lagirand-Cantaloube et al., 2009). MyoD is involved in skeletal muscle differentiation and maintenance of differentiated myotubes (Lagirand-Cantaloube et al., 2009). The protein level of MyoD gets heavily depleted in various models of muscle atrophy and overexpression of a mutant MyoD that does not get ubiquitinylated protects against muscle atrophy in vivo (Lagirand-Cantaloube et al., 2009). Ablation or depletion of MuRF1 and atrogin-1 alone or in combination have been shown to protect against skeletal muscle atrophy against various atrogenic stimuli (Bonaldo and Sandri, 2013). Forkhead box O (FoxO) family of transcription factors are the major positive regulators of both MuRF1 and atrogin-1 expression either via direct transcriptional regulation of atrogin-1 (Sandri et al., 2004) or via an indirect pathway involving the upregulation of the myokine myostatin that inhibits myogenesis (Lokireddy et al., 2011). FoxO proteins, in particular FoxO1 transcription is enhanced in different atrophy models (Lecker et al., 2004). On the other hand, the FoxO group of transcription factors are deactivated by PI3K/AKT signaling and activation of AKT prevents muscular atrophy (Sandri et al., 2004, Stitt et al., 2004). PGC-1α, a transcriptional coactivator expressed highly in tissues with high energy demand has been shown to undergo robust downregulation in various forms of muscle atrophy and its overexpression counters the effect of FoxO on muscle mass, via downregulation of atrogenes (Sandri et al., 2006). In addition to Atrogin-1 and MuRF1, lysosomal protease cathepsin L has also been implicated in various forms of muscle atrophy including fasting and glucocorticoid-induced muscle atrophy where its expression is upregulated (Sacheck et al., 2007, Lecker et al., 2004, Deval et al., 2001). FoxO1 has been reported as a direct activator of cathepsin L transcription (Yamazaki et al., 2010).