Up-regulation of Vps4A promotes neuronal apoptosis after intracerebral hemorrhage in adult rats

Metab Brain Dis. 2017 Apr;32(2):565-575. doi: 10.1007/s11011-016-9943-6. Epub 2017 Jan 7.

Abstract

Vps4, vacuolar protein sorting 4, belongs to ATPases Associated with diverse cellular Activities (AAA) protein family which is made up of Vps4A and Vps4B. Previous studies demonstrated that Vps4A plays vital roles in diverse aspects such as virus budding, the efficient transport of H-Ras to the PM (plasma membrane) and the involvement in the MVB (multivesiculate bodies) pathway. Interestingly, Vps4A is also expressed in the brain. However, the distribution and function of Vps4A in ICH diseases remain unclear. In this study, we show that Vps4A may be involved in neuronal apoptosis during pathophysiological processes of intracerebral hemorrhage (ICH). Based on the results of Western blot and immunohistochemistry, we found a remarkable up-regulation of Vps4A expression surrounding the hematoma after ICH. Double labeled immunofluorescence showed that Vps4A was co-expressed with NeuN but rarely with astrocytes and microglia. Morever, we detected that neuronal apoptosis marker active caspase-3 had co-localizations with Vps4A. Additionaly, Vps4A knockdown in vitro specifically leads to decreasing neuronal apoptosis coupled with increased Akt phosphorylation. All datas suggested that Vps4A was involved in promoting neuronal apoptosis via inhibiting Akt phosphorylation after ICH.

Keywords: Apoptosis; Intracerebral hemorrhage; Neuron; Vps4A.

MeSH terms

  • ATPases Associated with Diverse Cellular Activities / biosynthesis*
  • Animals
  • Antigens, Nuclear / metabolism
  • Apoptosis / drug effects*
  • Behavior, Animal / drug effects
  • Caspase 3 / metabolism
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / psychology
  • Female
  • Gene Knockdown Techniques
  • Male
  • Nerve Tissue Proteins / metabolism
  • Oncogene Protein v-akt / metabolism
  • Phosphorylation
  • Pregnancy
  • Primary Cell Culture
  • Rats
  • Rats, Sprague-Dawley
  • Up-Regulation / drug effects
  • Vacuolar Proton-Translocating ATPases / biosynthesis*

Substances

  • Antigens, Nuclear
  • Nerve Tissue Proteins
  • Rbfox3 protein, rat
  • Oncogene Protein v-akt
  • Casp3 protein, rat
  • Caspase 3
  • Vps4A protein, rat
  • Vacuolar Proton-Translocating ATPases
  • ATPases Associated with Diverse Cellular Activities