TCA cycle metabolic compromise due to an aberrant S-nitrosoproteome in HIV-associated neurocognitive disorder with methamphetamine use.

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  • Additional Information
    • Source:
      Publisher: Springer Country of Publication: United States NLM ID: 9508123 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-2443 (Electronic) Linking ISSN: 13550284 NLM ISO Abbreviation: J Neurovirol Subsets: MEDLINE
    • Publication Information:
      Publication: 2011- : New York : Springer
      Original Publication: Houndmills, Basingstoke, Hampshire ; New York, NY : Stockton Press, c1995-
    • Subject Terms:
      Protein Processing, Post-Translational*; Citric Acid Cycle/*drug effects ; Cognitive Dysfunction/*metabolism ; HIV Infections/*metabolism ; Methamphetamine/*adverse effects ; Substance-Related Disorders/*metabolism; Autopsy ; Biological Specimen Banks ; Brain/drug effects ; Brain/enzymology ; Brain/pathology ; Citric Acid Cycle/genetics ; Cognitive Dysfunction/complications ; Cognitive Dysfunction/pathology ; Cognitive Dysfunction/virology ; Cysteine/analogs & derivatives ; Cysteine/metabolism ; HIV Infections/complications ; HIV Infections/pathology ; HIV Infections/virology ; HIV-1/growth & development ; HIV-1/pathogenicity ; Humans ; Male ; Middle Aged ; Mitochondria/drug effects ; Mitochondria/enzymology ; Mitochondria/pathology ; Neurons/drug effects ; Neurons/enzymology ; Neurons/pathology ; Nitric Oxide/metabolism ; S-Nitrosothiols/metabolism ; Substance-Related Disorders/complications ; Substance-Related Disorders/pathology ; Substance-Related Disorders/virology ; Synapses/drug effects ; Synapses/pathology
    • Abstract:
      In the brain, both HIV-1 and methamphetamine (meth) use result in increases in oxidative and nitrosative stress. This redox stress is thought to contribute to the pathogenesis of HIV-associated neurocognitive disorder (HAND) and further worsening cognitive activity in the setting of drug abuse. One consequence of such redox stress is aberrant protein S-nitrosylation, derived from nitric oxide, which may disrupt normal protein activity. Here, we report an improved, mass spectrometry-based technique to assess S-nitrosylated protein in human postmortem brains using selective enrichment of S-nitrosocysteine residues with an organomercury resin. The data show increasing S-nitrosylation of tricarboxylic acid (TCA) enzymes in the setting of HAND and HAND/meth use compared with HIV+ control brains without CNS pathology. The consequence is systematic inhibition of multiple TCA cycle enzymes, resulting in energy collapse that can contribute to the neuronal and synaptic damage observed in HAND and meth use.
    • Comments:
      Erratum in: J Neurovirol. 2021 May 3;:. (PMID: 33942273)
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    • Grant Information:
      R01 AG061845 United States AG NIA NIH HHS; U24 MH100928 United States MH NIMH NIH HHS; R01 AG056259 United States AG NIA NIH HHS; RF1 AG057409 United States AG NIA NIH HHS; R01 NS086890 United States NS NINDS NIH HHS; DP1 DA041722 United States DA NIDA NIH HHS
    • Contributed Indexing:
      Keywords: HIV-1; Methamphetamine; Mitochondrial dysfunction; Protein S-nitrosylation; TCA cycle
    • Accession Number:
      0 (S-Nitrosothiols)
      31C4KY9ESH (Nitric Oxide)
      44RAL3456C (Methamphetamine)
      926P2322P4 (S-nitrosocysteine)
      K848JZ4886 (Cysteine)
    • Publication Date:
      Date Created: 20210420 Date Completed: 20220121 Latest Revision: 20240229
    • Publication Date:
      20240229
    • Accession Number:
      PMC8477648
    • Accession Number:
      10.1007/s13365-021-00970-4
    • Accession Number:
      33876414