Exosome-mediated shuttling of microRNA-29 regulates HIV Tat and morphine-mediated Neuronal dysfunction

G. Hu, H. Yao, A. D. Chaudhuri, M. Duan, S. V. Yelamanchili, H. Wen, P. D. Cheney, H. S. Fox, S. Buch

Research output: Contribution to journalArticle

105 Scopus citations

Abstract

Neuronal damage is a hallmark feature of HIV-associated neurological disorders (HANDs). Opiate drug abuse accelerates the incidence and progression of HAND; however, the mechanisms underlying the potentiation of neuropathogenesis by these drugs remain elusive. Opiates such as morphine have been shown to enhance HIV transactivation protein Tat-mediated toxicity in both human neurons and neuroblastoma cells. In the present study, we demonstrate reduced expression of the tropic factor platelet-derived growth factor (PDGF)-B with a concomitant increase in miR-29b in the basal ganglia region of the brains of morphine-dependent simian immunodeficiency virus (SIV)-infected macaques compared with the SIV-infected controls. In vitro relevance of these findings was corroborated in cultures of astrocytes exposed to morphine and HIV Tat that led to increased release of miR-29b in exosomes. Subsequent treatment of neuronal SH-SY5Y cell line with exosomes from treated astrocytes resulted in decreased expression of PDGF-B, with a concomitant decrease in viability of neurons. Furthermore, it was shown that PDGF-B was a target for miR-29b as evidenced by the fact that binding of miR-29 to the 3′-untranslated region of PDGF-B mRNA resulted in its translational repression in SH-SY5Y cells. Understanding the regulation of PDGF-B expression may provide insights into the development of potential therapeutic targets for neuronal loss in HIV-1-infected opiate abusers.

Original languageEnglish (US)
Article numbere375
JournalCell Death and Disease
Volume3
Issue number8
DOIs
StatePublished - Aug 1 2012

    Fingerprint

Keywords

  • HAND
  • MiRNA
  • Morphine
  • Neuronal dysfunction
  • PDGF-B

ASJC Scopus subject areas

  • Immunology
  • Cellular and Molecular Neuroscience
  • Cell Biology
  • Cancer Research

Cite this