AMP-activated protein kinase–dependent prostaglandin pathway (AMPK-PG pathway)

The AMP-activated protein kinase (AMPK)-dependent prostaglandin pathway is a regulatory signaling axis that integrates cellular energy status with the production of pro-inflammatory lipid mediators. AMPK, a master metabolic switch, modulates this pathway primarily by inhibiting the expression and activity of cyclooxygenase-2 (COX-2), the rate-limiting enzyme in the synthesis of prostaglandins such as PGE2 (Hwang et al., 2002; PubMed: 12140560). Activation of AMPK typically exerts anti-inflammatory and anti-neoplastic effects by downregulating pro-survival prostanoid signaling, which is often overactive in chronic inflammatory states and various cancers (Park et al., 2007; PubMed: 17339483). This pathway is a significant therapeutic target for metabolic-based anti-inflammatory strategies, as drugs like metformin and salicylates have been shown to reduce inflammation and tumor growth by activating AMPK and subsequently suppressing COX-2-mediated prostaglandin production (Hawley et al., 2012; PubMed: 22517326). Understanding this axis provides insights into how metabolic reprogramming can be leveraged to treat diseases driven by chronic inflammation and aberrant cell proliferation.

Other names

AMPK-COX-2 axisAMPK-prostanoid signaling pathwayAMPK-mediated prostaglandin regulationAMPK-dependent COX-2 pathway

Activation of AMPK leads to the transcriptional and post-translational downregulation of COX-2 expression and activity, resulting in decreased synthesis of pro-inflammatory prostaglandins.