Anti-SIRT1 Antibody (A29757)

MicroRNA‑34a (miR‑34a) is a direct target of p53 and was reported to induce cell cycle arrest, apoptosis and senescence. Inhibition of the NAD‑dependent deacetylase sirtuin‑1 (SIRT1) by miR‑34a leads to an increase in acetylated p53, which promotes cell apoptosis. B‑cell lymphoma 2 (Bcl‑2) is also involved in apoptosis, and was originally characterized with respect to its role in controlling outer mitochondrial membrane integrity. The effect of miR‑34a in PC12 cells has not yet been reported. In the present study, it was hypothesized that Bcl‑2 and SIRT1 may be critical downstream targets of miR‑34a that participate in apoptosis induction. miR‑34a mimics and inhibitors were transfected into PC12 cells, and the apoptosis and proliferation rates were compared between groups. It was demonstrated that induction of miR‑34a promotes apoptosis and senescence, inhibits proliferation, and leads to marked alterations in SIRT1, Bcl‑12 and acetyl (ac)‑p53 expression. These data indicate that miR‑34a may be important in neuropathy.

AIMS:

Anemia of inflammation is quite prevalent in hospitalized patients with poor prognosis. Concerns about the effectiveness and safety of iron supplementation have arisen, driving the demand for alternative therapies. Induction of hepatic hepcidin, the master hormone of iron homeostasis, causes anemia under inflammatory conditions. Previous studies indicated that hydrogen sulfide (H2S), the third gasotransmitter and a well-known regulator of inflammation, may inhibit the secretion of inflammatory cytokines. We thus investigated the effect of H2S on inflammatory hepcidin induction.

RESULTS:

H2S suppressed lipopolysaccharide (LPS)-induced hepcidin production and regulated iron homeostasis in mice by decreasing serum interleukin-6 (IL-6) and Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) activation; similar results were obtained in Huh7 cells exposed to conditioned medium from LPS-challenged THP-1 macrophages. Intriguingly, we found H2S also attenuated hepcidin levels in Huh7 cells and mouse primary hepatocytes in a sirtuin 1 (SIRT1)-dependent manner. By promoting SIRT1 expression and stabilizing SIRT1-STAT3 interactions, H2S ameliorated IL-6-induced STAT3 acetylation, resulting in reduced hepcidin production. Inhibition and silencing of SIRT1 diminished H2S-mediated suppression of hepcidin, as opposed to SIRT1 activation and overexpression. Consistent results were observed in vivo. Furthermore, knockout of cystathionine γ-lyase (CSE), an endogenous H2S synthase, exaggerated inflammatory hepcidin expression in mice.

INNOVATION:

For the first time, we elucidated the effects and possible mechanisms of H2S on inflammatory hepcidin and established a novel regulatory link between SIRT1 and hepcidin.

CONCLUSION:

Our work demonstrates that H2S attenuates inflammation-induced hepatic hepcidin via multipathways and suggests new treatment strategies for anemia of inflammation.

Granulocyte/macrophage colony-stimulating factor (GM-CSF) can accelerate wound healing by promoting angiogenesis. The biological effects of GM-CSF in angiogenesis and the corresponding underlying molecular mechanisms, including in the early stages of primitive endothelial tubule formation and the later stages of new vessel maturation, have only been partially clarified. This study aimed to investigate the effects of GM-CSF on angiogenesis and its regulatory mechanisms. Employing a self-controlled model (Sprague-Dawley rats with deep partial-thickness burn wounds), we determined that GM-CSF can increase VEGF expression and decrease the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 in the early stages of the wound healing process, which promotes the degradation of the basement membrane and the proliferation of endothelial cells. At later stages of wound healing, GM-CSF can increase the expression ratio of Ang-1/Ang-2 and the phosphorylation of Tie-2 and maintain a high VEGF expression level. Consequently, pericyte coverages were higher, and the basement membrane became more integrated in new blood vessels, which enhanced the barrier function of blood vessels. In summary, we report here that increased angiogenesis is associated with GM-CSF treatment, and we indicate that VEGF and the Ang/Tie system may act as angiogenic mediators of the healing effect of GM-CSF on burn wounds.