[Objectives] Alternative splicing alters protein structure, localization and function and increases biological diversity in response to physiological and pathological stress conditions. We investigated how alternative splicing of titin, CaMKII δ and ZASP/Cypher genes changes in hearts under pathological stress conditions. [Methods] The alternative splicing of titin, CaMKII δ and ZASP/Cypher genes, in response to acute inflammation, pressure overload and hypoxia, was analyzed by quantitative RT-PCR in the hearts of experimental autoimmune myocarditis rats and myocarditis patients, monocrotaline pulmonary hypertension rats and in cardiomyocytes cultured under hypoxic conditions. [Results] Large N2BA-titin, cytoplasmic CaMKII δ and PGM1-binding ZASP/Cypher isoforms significantly increased in rat hearts with myocarditis and hypertrophy compared with normal hearts. Large N2BA-titin and cytoplasmic CaMKII δ isoforms also significantly increased in myocarditis patient hearts compared with those with DCM. In cardiomyocytes under hypoxic conditions, PGM1-binding ZASP/Cypher isoforms significantly increased, but large N2BA-titin and cytoplasmic CaMKII δ isoforms decreased, compared with cells under normoxic conditions. [Conclusions] The alternative splicing of titin, CaMKII δ and ZASP/Cypher genes was markedly modulated in hearts under pathological stress conditions and may be involved in adaptations to pathological changes.
心疾患におけるtitin, CaMKIIδおよびZASP/Cypher mRNAの選択的スプライシングの調節
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