Pinocembrin Relieves Mycoplasma pneumoniae Infection­Induced Pneumonia in Mice Through the Inhibition of Oxidative Stress and Inflammatory Response.

Pneumonia is a serious infectious disease with increased morbidity and mortality worldwide. The M. pneumoniae is a major airway pathogen that mainly affects respiratory tract and ultimately leads to the development of pneumonia. The current exploration was aimed to uncover the beneficial properties of pinocembrin against the M. pneumoniae-triggered pneumonia in mice via its anti-inflammatory property. The pneumonia was stimulated to the BALB/c mice via infecting them with M. pneumoniae (100 µl) for 2 days through nasal drops and concomitantly treated with pinocembrin (10 mg/kg) for 3 days. The azithromycin (100 mg/kg) was used as a standard drug. Then the lung weight, nitric oxide, and myeloperoxidase (MPO) activity was assessed. The content of MDA, GSH, and SOD activity was scrutinized using kits. The total cells and DNA amount present in the bronchoalveolar lavage fluid (BALF) was assessed by standard methods. The IL-1, IL-6, IL-8, TNF-α, and TGF contents in the BALF samples and NF-κB level in the lung tissues were assessed using kits. The lung histopathology was assessed microscopically to detect the histological alterations. The 10 mg/kg of pinocembrin treatment substantially decreased the lung weight, nitric oxide (NO) level, and MPO activity. The MDA level was decreased, and GSH content and SOD activity were improved by the pinocembrin treatment. The pinocembrin administered pneumonia animals also demonstrated the decreased total cells, DNA amount, IL-1, IL-6, IL-8, TNF-α, and TGF in the BALF and NF-κB level. The findings of histological studies also witnessed the beneficial role of pinocembrin against M. pneumoniae-infected pneumonia. In conclusion, our findings confirmed that the pinocembrin effectively ameliorated the M. pneumoniae-provoked inflammation and oxidative stress in the pneumonia mice model. Hence, it could be a hopeful therapeutic agent to treat the pneumonia in the future.

Geranylgeranyltransferase I regulates HIF-1α promoting glioblastoma cell migration and invasion.

Glioblastoma multiforme is a highly migratory and invasive brain tumor in which hypoxia inducible factor-1α (HIF-1α) plays important roles. However, the underlying mechanisms regulating the action of HIF-1α in glioma cell migration and invasion ability remain unclear. We reported here that HIF-1α was regulated by geranylgeranyltransferase I (GGTI), a protein prenylation transferase, and then promoted glioma cell migration and invasion. The migratory and invasive ability of glioma cells were enhanced by hypoxia treatment but inhibited by down-regulation of HIF-1α. GGTI activity inhibition or GGTI specific ß subunit (GGTI ß) knocking-down decreased HIF-1α protein level. In addition, down-regulation of GGTI ß inhibited migration and invasion of glioma cells under hypoxia, while GGTI ß over-expression promoted it. Furthermore, the effect of GGTI ß over-expression on cell migration and invasion was abolished by HIF-1α down-regulation. In summary, our study showed, for the first time, that HIF-1α was regulated by protein prenylation transferase GGTI and mediated the effect of GGTI on glioma cell migration and invasion.

Geranylgeranyltransferase I promotes human glioma cell growth through Rac1 membrane association and activation.

Geranylgeranyltransferase I (GGTase-I) is responsible for the posttranslational lipidation of several signaling proteins such as RhoA, Rac1, and Cdc42, which contribute to tumor development and metastasis. However, the role of GGTase-I in the progression of human glioma is largely unknown. Here, we provide the evidence that Rac1 mediates the effects of GGTase-I on the proliferation and apoptosis in human glioma cells. We found that GGTase-I was abundantly expressed in human primary glioma tissues. Inhibition or downregulation of GGTase-I markedly decreased the proliferation of glioma cells and induced their apoptosis, while overexpression of GGTase-I promoted cell growth in vitro. Inactivation of GGTase-I eliminated geranylgeranylation of RhoA and Rac1, prevented them from targeting to the plasma membrane, and inhibited Rac1 activity. Furthermore, overexpressing wild type or constitutively active Rac1 stimulated glioma cell growth, similar to the effect of GGTase-I overexpression. Importantly, overexpressing dominant-negative Rac1 or Rac1 with the prenylation site deleted or mutated abrogated GGTase-I-induced proliferation in glioma cells. These results confirm the view that geranylgeranylation is essential to the activity and localization of Rho family proteins and suggest that Rac1 is required for GGTase-I-mediated glioma growth.