Adverse effects of cyclosporine A on HSP25, alpha-B crystallin and myofibrillar cytoskeleton in rat heart
Articolo
Data di Pubblicazione:
2009
Citazione:
Adverse effects of cyclosporine A on HSP25, alpha-B crystallin and myofibrillar cytoskeleton in rat heart / A. Stacchiotti, F. Bonomini, A. Lavazza, L.F. Rodella, R. Rezzani. - In: TOXICOLOGY. - ISSN 0300-483X. - 262:3(2009), pp. 192-198. [10.1016/j.tox.2009.06.007]
Abstract:
Cyclosporine (CsA) is a universally used immunosuppressive drug which induces adverse side effects in several organs, but its impact on the heart is still controversial.
Small heat shock proteins (sHSPs), such as HSP25 and alpha B-crystallin, are cytoprotective stress proteins exceptionally represented in the heart. They act as myofibrillar chaperones that help actin and desmin to maintain their optimum configuration and stability, thereby antagonizing oxidative damage.
The present study examined: (1) the cardiac distribution and abundance of HSP25 and alpha B-crystallin in rats receiving CsA at a therapeutic dosage (15 mg/kg/day) for 42 days and 63 days; (2) the presence of myofibrillar proteins, such as actin, alpha-actinin and desmin following the CsA treatments; (3) the
subcellular effects of prolonged CsA exposure on the cardiomyocytes by histopathology and transmission
electron microscopy. After 63 days CsA intake, sHSPs translocated from a regular sarcomeric pattern to
peripheral sarcolemma and intercalated discs, together with actin and desmin. In contrast, the sarcomeric alpha-actinin pattern did not change in all experimental groups. The abundance of actin and HSP25 was unchanged in every time point of treatment while after 63 days CsA, alpha B-crystallin and desmin levels
significantly decreased. Furthermore CsA induced fibrosis, irregular sarcomeric alignment and damaged desmosomes. These findings indicate that following prolonged CsA exposure, the cardiac muscle network was affected. In particular, the translocation of sHSPs to intercalated discs merits special consideration as a direct compensatory mechanism to limit CsA cardiotoxicity.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Cyclosporine A; Cytoskeleton; Heat shock proteins; Immunohistochemistry; Transmission electron microscopy
Elenco autori:
A. Stacchiotti, F. Bonomini, A. Lavazza, L.F. Rodella, R. Rezzani
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