AIMS: To investigate the role of TH (thyroid hormones) in 5'-nucleotidase activity and expression in cardiac soluble fraction (SF). MAIN METHODS: Male Wistar rats received daily injections of T4 (10, 25 or 50 μg T4/100g body weight) for 14 days to develop a hyperthyroidism condition. Thyroidectomy was performed in other animals to mimic hypothyroidism, and 14 days after surgery they were submitted to TH replacement therapy. KEY FINDINGS: T4 reduced the 5'-nucleotidase activity (T4-25, P<0.05 and T4-50, P<0.01) in the SF. Conversely, hypothyroidism significantly increased the 5'-nucleotidase activity in this fraction (P<0.001) and TH replacement therapy reversed the latter result (P<0.001 compared to hypothyroid group). The analysis of protein expression in the SF showed that 5'-nucleotidase was more expressed in hypothyroid than in the control group and that the phosphorylated state of PKC observed in this condition may contribute to a possible mechanism of 5'-nucleotidase modulation by thyroid status. SIGNIFICANCE: Taken together, these data reveal that TH can influence adenosine production by modulating 5'-nucleotidase activity and expression, which may contribute to the cardioprotective effect and the maintenance of cardiac function under TH privation.
AIMS: To investigate the role of TH (thyroid hormones) in 5'-nucleotidase activity and expression in cardiac soluble fraction (SF). MAIN METHODS: Male Wistar rats received daily injections of T4 (10, 25 or 50 μg T4/100g body weight) for 14 days to develop a hyperthyroidism condition. Thyroidectomy was performed in other animals to mimic hypothyroidism, and 14 days after surgery they were submitted to TH replacement therapy. KEY FINDINGS: T4 reduced the 5'-nucleotidase activity (T4-25, P<0.05 and T4-50, P<0.01) in the SF. Conversely, hypothyroidism significantly increased the 5'-nucleotidase activity in this fraction (P<0.001) and TH replacement therapy reversed the latter result (P<0.001 compared to hypothyroid group). The analysis of protein expression in the SF showed that 5'-nucleotidase was more expressed in hypothyroid than in the control group and that the phosphorylated state of PKC observed in this condition may contribute to a possible mechanism of 5'-nucleotidase modulation by thyroid status. SIGNIFICANCE: Taken together, these data reveal that TH can influence adenosine production by modulating 5'-nucleotidase activity and expression, which may contribute to the cardioprotective effect and the maintenance of cardiac function under TH privation.
Authors: Vicki E Smith; Christopher J McCabe; Alice Fletcher; Martin L Read; Caitlin E M Thornton; Dean P Larner; Vikki L Poole; Katie Brookes; Hannah R Nieto; Mohammed Alshahrani; Rebecca J Thompson; Gareth G Lavery; Iñigo Landa; James A Fagin; Moray J Campbell; Kristien Boelaert; Andrew S Turnell Journal: Cancer Res Date: 2019-10-31 Impact factor: 12.701