Direct Peritoneal Resuscitation with Pyruvate Protects the Spinal Cord and Induces Autophagy via Regulating PHD2 in a Rat Model of Spinal Cord Ischemia-Reperfusion Injury

Figure 1

PHDs could hydroxylate HIF-1α under normoxia, and the latter is discerned by the von Hippel-Lindau (VHL) tumor suppressor protein and then degraded by the proteasome. Under hypoxic conditions, HIF-1α is stabilized due to inactivation of PHDs, and then BNIP3 is upregulated as the direct target of HIF-1α. Upregulation of BNIP3 will bind to Rheb which would inhibit mTOR signaling and competing with Beclin-1-Bcl-2 and Beclin-1-Bcl-xl complexes allowing the release of Beclin-1. Autophagy would be enhanced via both sides, eventually, reducing inhibition of autophagy and enhancing activation of autophagy. Meanwhile, under hypoxia, accumulation of HIF-1α can induce the transcription of PHD2, in contrast, to ensure swift removal of HIF-1α after reoxygenation.