Oxidative inactivation of the lipid phosphatase phosphatase and tensin homolog on chromosome ten (PTEN) as a novel mechanism of acquired long QT syndrome.

ABSTRACT: The most common cause of cardiac side effects of pharmaco-therapy is acquired long QT syndrome, which is characterized by abnormal cardiac repolarization and most often caused by direct blockade of the cardiac potassium channel human ether a-go-go-related gene (hERG). However, little is known about therapeutic compounds that target ion channels other than hERG. We have discovered that arsenic trioxide (As(2)O(3)), a very potent antineoplastic compound for the treatment of acute promyelocytic leukemia, is proarrhythmic via two separate mechanisms: a well characterized inhibition of hERG/I(Kr) trafficking and a poorly understood increase of cardiac calcium currents. We have analyzed the latter mechanism in the present study using biochemical and electrophysiological methods. We find that oxi

SUBMITTER: Wan X 

PROVIDER: S-EPMC3024780 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature