Effect of histone H1 on the cytosolic calcium levels in human breast cancer MCF 7 cells.
In human breast cancer MCF 7 cells, the effect of exogenous histone H1 on intracellular calcium ([Ca2+]i) levels was measured using Fura 2AM. The dose and time dependent assessment revealed significant cell killing effect of histone H1 on MCF 7 cells. Histone H1 induced a sustained concentration dependent increase in [Ca2+]i levels in the presence of calcium in the medium, but the increase was reduced in the absence of extra cellular calcium. The effect of histone H1 on intracellular calcium flux measured using 45Ca radiolabel revealed significant inhibition of calcium uptake in endoplasmic reticulum, whereas the rate of uptake was unaltered in the mitochondria. The activities of phospholipase A2 showed a significant transient increase at 1 minute which by the end of 5 minutes decreased, whereas the activities of phospholipase C which showed a transient increase at the end of 1 minute, was maintained at basal levels in histone H1 treated cells compared to control cells. These findings suggest that histone H1 increases [Ca2+]i in MCF 7 cells by stimulating both extra cellular calcium influx and intracellular calcium release at higher concentrations exhibiting cytotoxic effect.
Ganapathy
Vani
V
Department of Biochemistry, University of Madras, Guindy campus, Chennai-600 025, India.
Shyamala Devi
Chennam Srinivasulu
CS
D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005260:Female; D006657:Histones / Q000494:pharmacology*; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010738:Type C Phospholipases / Q000378:metabolism
D006657:Histones; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D002118:Calcium