Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophils

Charp, Paul A.; Rice, William G.; Raynor, Robert L.; Reimund, Eric; Kinkade, Joseph M.; Ganz, T; Selsted, Michael E.; Lehrer, Robert I.; Kuo, J.F.

doi:10.1016/0006-2952(88)90187-6

Cited by 80 publications

(27 citation statements)

References 20 publications

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“…Our data show that ␣-defensin interacts with intracellular PKC; the data of Charp et al 31 indicate that this interaction leads to inhibition of the enzyme. To confirm that inhibition of PKC is sufficient to induce inhibition of PE-induced SMC contraction, we examined the effect of other known inhibitors of PKC.…”

Section: Resultssupporting

confidence: 66%

“…Charp et al found that ␣-defensin inhibits the activity of PKC. 31 It is widely accepted that PKC plays an important role in the contraction of SMCs; in the case of cerebral vasospasm, PKC is considered to have a significant role by phosphorylating various ion channels and augmenting voltage-dependent Ca ϩϩ channels, which leads to vessel contraction. 32 PKC has also been reported to enhance Ca V 1.2b channel currents in various SMC preparations.…”

Section: Resultsmentioning

confidence: 99%

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Human α-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor–related protein/α2-macroglobulin receptor

Nassar

Akkawi

Bar-Shavit

et al. 2002

Blood

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Section: Resultssupporting

confidence: 66%

Section: Resultsmentioning

confidence: 99%

Human α-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor–related protein/α2-macroglobulin receptor

Nassar

Akkawi

Bar-Shavit

et al. 2002

Blood

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“…α-Defensin-1 can inhibit PKC in vitro (39). In addition, it is internalized and interacts with PKCα and β in smooth muscle cells (40).…”

Section: Resultsmentioning

confidence: 99%

Dual role of α-defensin-1 in anti–HIV-1 innate immunity

Chang¹,

Vargas²,

DelPortillo³

et al. 2005

J. Clin. Invest.

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α-Defensins are abundant antimicrobial peptides in polymorphonuclear leukocytes and play an important role in innate immunity. We have previously shown that α-defensin-1 can inhibit HIV-1 replication following viral entry. Here we examined the molecular mechanism(s) of α-defensin-1-mediated HIV-1 inhibition. α-Defensin-1 had a direct effect on HIV-1 virions at a low MOI in the absence of serum. The direct effect on HIV-1 virions was abolished by the presence of serum or an increase in virus particles. Studying the kinetics of the HIV life cycle revealed that α-defensin-1 inhibited steps following reverse transcription and integration. Analysis of PKC phosphorylation in primary CD4 + T cells in response to α-defensin-1 indicated that α-defensin-1 inhibited PKC activity. Pretreatment of infected CD4 + T cells with a PKC activator, bryostatin 1, partially reversed α-defensin-1-mediated HIV inhibition. Like α-defensin-1, the PKC isoform-selective inhibitor Go6976 blocked HIV-1 infection in a dose-dependent manner. Furthermore, kinetic studies and analysis of HIV-1 products indicated that α-defensin-1 and Go6976 blocked HIV-1 infection at similar stages in its life cycle, including nuclear import and transcription. Taken together, our studies demonstrate that, in the absence of serum, α-defensin-1 may act directly on the virus, but, in the presence of serum, its effects are on the cell, where it inhibits HIV-1 replication. At least 1 of the cellular effects associated with HIV inhibition is interference with PKC signaling in primary CD4 + T cells. Studying the complex function of α-defensin-1 in innate immunity against HIV has implications for prevention as well as therapeutics.

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“…The molecular mechanism of HIV inhibition remains unclear. It is known that defensins and peptides derived from HIV-1 gp41 (HIV Env 583 to 610) have similar structures and functions including binding to complement component C1q, complement activation, and protein kinase C (PKC) inhibition (4,27,35,37,38). Retrocyclin, a circular form of defensin, inhibits HIV-1 not through direct viral inactivation but at the steps prior to reverse transcription (8).…”

mentioning

confidence: 99%

CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from α-Defensin-1 HIV Inhibition

Chang

François

Mosoian

et al. 2003

J Virol

109

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Inhibition of protein kinase C by defensins, antibiotic peptides from human neutrophils

Cited by 80 publications

References 20 publications

Human α-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor–related protein/α2-macroglobulin receptor

Human α-defensin regulates smooth muscle cell contraction: a role for low-density lipoprotein receptor–related protein/α2-macroglobulin receptor

Dual role of α-defensin-1 in anti–HIV-1 innate immunity

CAF-Mediated Human Immunodeficiency Virus (HIV) Type 1 Transcriptional Inhibition Is Distinct from α-Defensin-1 HIV Inhibition

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