In:
Canadian Journal of Physiology and Pharmacology, Canadian Science Publishing, Vol. 69, No. 11 ( 1991-11-01), p. 1677-1685
Abstract:
Isolated rat hearts perfused with 100 μM hypochlorous acid (HOCl), a powerful oxidant produced by activated neutrophils, exhibited progressive impairment of contractile performance suggestive of a cytosolic Ca 2+ overload (increased left ventricular end-diastolic pressure, increased aortic root perfusion pressure, and depressed pulse pressure). Sarcoplasmic reticulum (SR) enriched microsomal preparations isolated from HOCl-perfused hearts showed a significant decline, when compared with control hearts, in both Ca 2+ ATPase activity (123 ± 40 vs. 473 ± 46 nmol P i ∙mg −1 protein∙min −1 ) and Ca 2+ uptake (12 ± 5 vs. 46 ± 4 nmol Ca 2+ ∙mg −1 protein∙min −1 ). The sulfhydryl content in Ca 2+ ATPase and other proteins, as determined by [ 14 C]iodoacetamide binding, was also progressively depleted in HOCl-perfused hearts. Perfusion of the HOCl-treated hearts with dithiothreitol (DTT), a disulfide reducing agent, resulted in a time-dependent attenuation, and eventual partial reversal, of the dysfunction in both contractility and SR Ca 2+ ATPase activity. Protein thiol levels were concomitantly restored to near control values. The data indicate that HOCl-induced contractile dysfunction in heart is related to the inactivation of the SR Ca 2+ ATPase as a result of thiol oxidation and suggest that DTT is capable of reversing this dysfunction in situ by reducing the oxidized sulfhydryls in the Ca 2+ ATPase.Key words: hypochlorous acid, dithiothreitol, cardiac sarcoplasmic reticulum, Ca 2+ ATPase, protein sulfhydryl.
Type of Medium:
Online Resource
ISSN:
0008-4212
,
1205-7541
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
1991
detail.hit.zdb_id:
2004356-9
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