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Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: I. In vitro cytotoxicity.

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Evidence in the literature suggests that hyperthermia (HT) or inhibitors of calmodulin can increase the sensitivity of rodent cells to bleomycin (BLM) by interfering with DNA repair functions. In an attempt to explore methods of improving the efficacy of thermochemotherapy we have investigated the

W-7, a calmodulin antagonist, and contracture of malignant hyperthermia susceptible skeletal muscle.

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1. In malignant hyperthermia susceptible muscle fibers, the calmodulin antagonist, W-7 (10 microM), evoked contractures and potentiated halothene (3%) induced contracture. No effect was seen at 0.1 or 1.0 microM) W-7. 2. Dantrolene sodium (6 microM) prevented and reversed W-7 induced contracture:

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumor cells.

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To improve the efficacy of thermochemotherapy we have investigated the individual and combined effects of hyperthermia (44 degrees C) and the calmodulin inhibitor trifluoperazine (30 micrograms/ml) on early plateau phase cultures of mouse EMT6 cells for simultaneous exposures to bleomycin. We found

Calmodulin sensitivity of the sarcoplasmic reticulum ryanodine receptor from normal and malignant-hyperthermia-susceptible muscle.

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Ca2+ release from sarcoplasmic reticulum (SR) of malignant-hyperthermia-susceptible (MHS) muscle is hypersensitive to Ca2+ and caffeine. To determine if an abnormal calmodulin (CaM) regulation of the SR Ca(2+)-release-channel-ryanodine-receptor complex (RYR1) contributes to this hypersensitivity, we

Interaction of bleomycin, hyperthermia and a calmodulin inhibitor (trifluoperazine) in mouse tumour cells: II. DNA damage, repair and chromatin changes.

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We have reported in the preceding paper that the treatment of plateau phase mouse EMT6 tumour cells with a combination of hyperthermia (HT; 44 degrees C) and trifluoperazine (TFP; 30 micrograms ml-1; an inhibitor of calmodulin) greatly enhances the cytotoxicity of the antitumour drug belomycin

Vimentin rearrangement during African swine fever virus infection involves retrograde transport along microtubules and phosphorylation of vimentin by calcium calmodulin kinase II.

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African swine fever virus (ASFV) infection leads to rearrangement of vimentin into a cage surrounding virus factories. Vimentin rearrangement in cells generally involves phosphorylation of N-terminal domains of vimentin by cellular kinases to facilitate disassembly and transport of vimentin

Affinity isolation of heat-shock and other calmodulin-binding proteins following hyperthermia.

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The interaction of calmodulin (CaM) with heat-shock and other binding proteins was studied in rat adenocarcinoma cells. Cells were equilibrium-labeled for 48 h prior to heating for 1 h at 43 degrees C, or pulse-labeled for 2 h at 37 degrees C after heating, to monitor the effect of heat on the

Malignant hyperthermia in pigs: a search for abnormalities in Ca2+ binding proteins.

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Malignant hyperthermia occurs in man and pigs as a hereditary disorder notably as a complication of halothane-induced anaesthesia. It involves an abnormality in the metabolism of Ca2+. A search was made for abnormalities of calcium-binding proteins. Troponin C from normal pig muscle was found to

Malignant hyperthermia: an inherited disorder of skeletal muscle Ca+ regulation.

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Malignant hyperthermia (MH) is a pharmacogenetic disorder of skeletal muscle characterized by muscle contracture and life-threatening hypermetabolic crisis following exposure to halogenated anesthetics and depolarizing muscle relaxants during surgery. Susceptibility to MH results from mutations in

A retinal heat shock protein is associated with elements of the cytoskeleton and binds to calmodulin.

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Elevation of body temperature to a level similar to that attained during fever induces a disaggregation of polysomes in the mammalian retina and induction of a 74K heat shock protein (hsp74). Induced retinal hsp74 copurifies with twice cycled microtubules and also with purified intermediate

Effects of ischemia on multifunctional calcium/calmodulin-dependent protein kinase type II in the gerbil.

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Cerebral ischemia produces a disruption of calcium homeostasis in neurons. This may explain the extreme sensitivity of these cells to ischemic insult. Prolonged increases in calcium levels may produce irreversible damage to the cell by altering important calcium-dependent enzyme systems such as

Temperature modulation of ischemic neuronal death and inhibition of calcium/calmodulin-dependent protein kinase II in gerbils.

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We used brief bilateral carotid artery occlusion in gerbils to examine the effects of temperature on ischemia-induced inhibition of calcium/calmodulin-dependent protein kinase II activity and neuronal death. In normothermic (36 degrees C) gerbils, ischemia induced a severe loss of hippocampal CA1

Functional characterization of a distinct ryanodine receptor mutation in human malignant hyperthermia-susceptible muscle.

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Malignant hyperthermia is an inherited autosomal disorder of skeletal muscle in which certain volatile anesthetics and depolarizing muscle relaxants trigger an abnormally high release of Ca2+ from the intracellular Ca2+ store, the sarcoplasmic reticulum. In about 50% of cases, malignant hyperthermia

Calmodulin inhibitors potentiate hyperthermic cell killing.

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The role of calmodulin (CaM) in cellular heat injury of neuroblastoma N2A and hepatoma H35 cells has been investigated, using specific calmodulin-inhibiting drugs (Trifluoperazine, Compound 48/80 and Calmidazolium). These CaM-specific drugs potentiate hyperthermia-induced cell killing, suggesting

Pharmacological distinction between dantrolene and ryanodine binding sites: evidence from normal and malignant hyperthermia-susceptible porcine skeletal muscle.

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Dantrolene inhibits and ryanodine stimulates calcium release from skeletal-muscle sarcoplasmic reticulum (SR), the former by an unknown mechanism, and the latter by activating the ryanodine receptor (RyR), the primary Ca2+-release channel of SR. Dantrolene is used to treat malignant hyperthermia

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