CD38/cyclic ADP-ribose regulates astrocyte calcium signaling: Implications for neuroinflammation and HIV-1-associated dementia

Sugato Banerjee, Timothy F. Walseth, Kathleen Borgmann, Li Wu, Keshore R. Bidasee, Mathur S. Kannan, Anuja Ghorpade

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

CD38 is a 45-kD ectoenzyme involved in the synthesis of potent calcium (Ca2+)-mobilizing agents, cyclic adenosine diphosphate-ribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP+). In HIV-1-infected patients, increased CD38 expression on CD8+ T cells is linked to immune system activation and progression of HIV-1 infection. However, the role of CD38 upregulation in astrocyte function and HIV-1-associated dementia (HAD-now called HAND: HIV-1-associated neurocognitive disorder) neuropathogenesis is unclear. To these ends, we used interleukin (IL)-1β and HIV-1gp120 to activate primary human astrocytes and measured CD38 expression using real-time polymerase chain reaction and CD38 function by ADP-ribosyl cyclase activity. We also determined cADPR-mediated changes in single-cell intracellular Ca2+ transients in activated astrocytes in presence or absence of ethylene glycol tetraacetic acid. CD38 levels were downregulated using CD38 small-interfering RNA (siRNA) and intracellular Ca2+ concentration ([Ca2+]i) was measured. We previously reported a ∼20-fold rise in CD38 messenger RNA levels in IL-1β-activated astrocytes. We extend this observation and report that HIV-1gp120 potentiated CD38 expression in a dose-dependent manner and also increased CD38 enzyme activity in control and IL-1β-activated astrocytes. We demonstrate higher cADPR levels in IL-1β-activated astrocytes with a corresponding rise in [Ca2+]i upon cADPR application and its non-hydrolysable analog, 3-deaza-cADPR. In activated astrocytes, pre-treatment with the cADPR-specific antagonist 8-Br-cADPR and CD38 siRNA transfection returned elevated [Ca2+]i to baseline, thus confirming a CD38-cADPR specific response. These data are important for unraveling the mechanisms underlying the role of astrocyte-CD38 in HAD and have broader implications in other inflammatory diseases involving astrocyte activation and CD38 dysregulation.

Original languageEnglish (US)
Pages (from-to)154-164
Number of pages11
JournalJournal of Neuroimmune Pharmacology
Volume3
Issue number3
DOIs
StatePublished - Sep 1 2008

Fingerprint

Cyclic ADP-Ribose
Calcium Signaling
Astrocytes
Dementia
HIV-1
Interleukin-1
Small Interfering RNA
ADP-ribosyl Cyclase
HIV
Egtazic Acid
HIV Infections
Transfection
Real-Time Polymerase Chain Reaction
Immune System
Up-Regulation
Down-Regulation
Calcium

Keywords

  • Astrocyte
  • CD38
  • Calcium
  • HIV-1-associated dementia
  • Neuroinflammation
  • cADPR

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Immunology and Allergy
  • Immunology
  • Pharmacology

Cite this

CD38/cyclic ADP-ribose regulates astrocyte calcium signaling : Implications for neuroinflammation and HIV-1-associated dementia. / Banerjee, Sugato; Walseth, Timothy F.; Borgmann, Kathleen; Wu, Li; Bidasee, Keshore R.; Kannan, Mathur S.; Ghorpade, Anuja.

In: Journal of Neuroimmune Pharmacology, Vol. 3, No. 3, 01.09.2008, p. 154-164.

Research output: Contribution to journalArticle

Banerjee, Sugato ; Walseth, Timothy F. ; Borgmann, Kathleen ; Wu, Li ; Bidasee, Keshore R. ; Kannan, Mathur S. ; Ghorpade, Anuja. / CD38/cyclic ADP-ribose regulates astrocyte calcium signaling : Implications for neuroinflammation and HIV-1-associated dementia. In: Journal of Neuroimmune Pharmacology. 2008 ; Vol. 3, No. 3. pp. 154-164.
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