4.3 Article

Hemin activation abrogates Mycoplasma hyorhinis replication in chronically infected prostate cancer cells via heme oxygenase-1 induction

Journal

FEBS OPEN BIO
Volume 11, Issue 10, Pages 2727-2739

Publisher

WILEY
DOI: 10.1002/2211-5463.13271

Keywords

heme oxygenase-1; host defense; infectious disease; innate immunity; Mycoplasma hyorhinis; prostate cancer

Funding

  1. FDA Program
  2. NIDCR Intramural Research Program

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Hemin has a significant inhibitory effect on the replication of M. hyorhinis in chronically infected prostate cancer cells, with over 90% inhibition. This effect is mediated through the induction of HO-1 protein expression, leading to increased intracellular levels of M. hyorhinis DNA. The study suggests that activated HO-1 has therapeutic potential in cellular innate responses against mycoplasma infection.
Mycoplasma hyorhinis (M. hyorhinis) lacks a cell wall and resists multiple antibiotics. We describe here the striking > 90% inhibitory effect of hemin, a natural inducer of the cytoprotective enzyme heme oxygenase-1 (HO-1), on M. hyorhinis replication in chronically infected LNCaP prostate cancer cells. The role of HO-1 in interrupting M. hyorhinis replication was confirmed by HO-1-specific siRNA suppression of hemin-induced HO-1 protein expression, which increased intracellular M. hyorhinis DNA levels in LNCaP cells. Proteomic analysis and transmission electron microscopy of hemin-treated cells confirmed the complete absence of M. hyorhinis proteins and intact microorganisms, respectively, strongly supporting these findings. Our study is the first to our knowledge suggesting therapeutic potential for activated HO-1 in cellular innate responses against mycoplasma infection.

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