Proplatelet formation in megakaryocytes is associated with endoplasmic reticulum stress

Genes Cells. 2016 Jul;21(7):798-806. doi: 10.1111/gtc.12384. Epub 2016 Jun 14.

Abstract

Although previous studies suggest that proplatelet formation in megakaryocytes involves caspase-3, the mechanism underlying the activation of caspase-3 is unknown. Here, we analyzed caspase activation in a human megakaryoblastic cell line, MEG-01, which forms proplatelets spontaneously. Specific activation of caspase-3 and caspase-4 was found in proplatelets. Consistent with previous observations of caspase-4 autoactivation in response to endoplasmic reticulum (ER) stress, several ER stress marker proteins were expressed during proplatelet formation. A pharmacological ER stressor enhanced platelet production via proplatelet formation, whereas inhibition of caspase-4 caused suppression. These results suggest that ER stress is a mechanism underlying the maturation of megakaryocytes.

MeSH terms

  • Apoptosis / genetics
  • Blood Platelets / metabolism
  • Caspase 3 / biosynthesis*
  • Caspase 3 / genetics
  • Caspases, Initiator / biosynthesis*
  • Caspases, Initiator / genetics
  • Cells, Cultured
  • Endoplasmic Reticulum Stress / genetics*
  • Gene Expression Regulation, Developmental
  • Humans
  • Megakaryocytes / metabolism*

Substances

  • CASP4 protein, human
  • Caspase 3
  • Caspases, Initiator