Calpain is involved in the HIV replication from the latently infected OM10.1 cells.
Treatment of OM10.1 cells latently infected with human immunodeficiency virus type 1 (HIV-1) with phorbol ester and calcium ionophore (A23187) induced virus replication which was blocked by N-Ac-Leu-Leu-norleucinal (ALLnL), a calpain inhibitor I, and not by lactacystin, a specific proteasome inhibitor. When the purified NF-kappa B/I kappa B complex was treated with mu-calpain, the specific DNA-binding activity was demonstrated by using electrophoretic mobility shift assay in vitro. This effect of mu-calpain was inhibited by ALLnL and calpastatin and not by lactacystin. In fact, we found that mu-calpain efficiently degraded I kappa B alpha. Furthermore, our Western blotting analysis has revealed that mu-calpain cleaves I kappa B alpha at its N-terminal and C-terminal regions that were previously reported to be involved in the interaction with NF-kappa B p65. These observations indicate that in monocyte/macrophage cells calcium signaling is involved in NF-kappa B activation through activation of calpain and thus calpain inhibitors may be effective in inhibiting the activation of latently infected HIV.
Teranishi
Futoshi
F
Department of Molecular Genetics, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan.
Liu
Zhen-Qiu
ZQ
Kunimatsu
Mitoshi
M
Imai
Kenichi
K
Takeyama
Hiromitsu
H
Manabe
Tadao
T
Sasaki
Makoto
M
Okamoto
Takashi
T
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001665:Binding Sites; D000001:Calcimycin / Q000494:pharmacology; D020013:Calcium Signaling; D002135:Calcium-Binding Proteins / Q000494:pharmacology; D002154:Calpain / Q000494:pharmacology / Q000502:physiology*; D002460:Cell Line; D006023:Glycoproteins / Q000494:pharmacology; D015497:HIV-1 / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D020672:I-kappa B Proteins / Q000737:chemistry / Q000378:metabolism; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects / Q000502:physiology*
D002135:Calcium-Binding Proteins; D006023:Glycoproteins; D020672:I-kappa B Proteins; D007476:Ionophores; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D011993:Recombinant Fusion Proteins; C116500:acetyl-leucinal-nor-leucinal; C039304:calpain inhibitors; C067713:lactacystin; D000072000:NF-KappaB Inhibitor alpha; D000001:Calcimycin; C033668:calpastatin; D002154:Calpain; C449002:mu-calpain; D007930:Leucine; D013755:Tetradecanoylphorbol Acetate; D000111:Acetylcysteine