The Ca(2+) / CaMKK2 Axis Mediates the Telbivudine Induces Upregulation of Creatine Kinase: Implications for mechanism of Antiviral Nucleoside Analogs Side Effect.

The Ca(2+) / CaMKK2 Axis Mediates the Telbivudine Induces Upregulation of Creatine Kinase: Implications for mechanism of Antiviral Nucleoside Analogs Side Effect. Biochem Pharmacol. 2017 Oct 13;: Authors: Jianfei L, Min W, Chunlai M, Bicui C, Jiming Z, Bin W Abstract Telbivudine (LdT), a widely prescribed anti-hepatitis B virus (HBV) drug for the treatment of chronic Hepatitis B (CHB), causes adverse reactions ranging from creatine kinase (CK) elevation to myopathy. The purpose of this study was to explore the mechanism(s) of LdT induced CK elevation. The effects of LdT on mitochondrial morphology and proteins (TK2 and β-actin), oxidative stress, intracellular Ca(2+) levels, Ca(2+)-related signaling pathway (CaMKK2/AMPK), and Ca(2+)-related biomarkers such as superoxide dismutase (SOD) and malondialdehyde (MDA) were assessed in human skeletal muscle cells (HSKMCs). The results showed that LdT induced a dose-dependent increase in CK activity in HSKMCs, without affecting mitochondrial morphology, and TK2 and β-actin protein levels, following 72h of treatment. In addition, LdT increased Ca(2+) production, ROS generation, MDA and lipid peroxide (LPO) levels, and activated the CaMKK2/AMPK signaling pathway. Moreover, these effects were attenuated by the BAPIA-AM (the calcium chelator). We also confirmed the presence of relevant markers (MDA, LPO, and SOD) in serum from CHB patients after LdT treatment, and found that CK was positively c...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Biochem Pharmacol Source Type: research