Abstract:
:The effect of the myotoxic drug chlorpromazine was studied in vitro on proteins of sarcoplasmic reticulum and mitochondrial matrix of skeletal muscle in the normal mouse. Our results indicate that the drug is specific for calcium-binding proteins (calcium ATPase, calsequestrin and calmitine). Its proteolytic effect on these proteins, apparently due to the stimulation of specific proteases, could account for its myotoxic action. Moreover, calsequestrin (sarcoplasmic reticulum) and calmitine (mitochondrial matrix) were not sensitive to the same proteases. Proteases acting on calmitine were inhibited by alpha 2-macroglobulin but not those acting on calsequestrin. Despite some similarities between these two proteins, their characteristics of localization and sensitivity of their proteases indicate that calmitine has a specificity within the mitochondrial matrix and very probably plays a major role in the mitochondrial regulation of free calcium, which controls the activity of various enzymes of the mitochondrial matrix involved in ATP synthesis.
journal_name
FEBS Lettjournal_title
FEBS lettersauthors
Lucas-Heron B,Le Ray B,Schmitt Ndoi
10.1016/0014-5793(95)01122-usubject
Has Abstractpub_date
1995-11-06 00:00:00pages
309-11issue
3eissn
0014-5793issn
1873-3468pii
0014-5793(95)01122-Ujournal_volume
374pub_type
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