Prohibitin-1 Is a Dynamically Regulated Blood Protein With Cardioprotective Effects in Sepsis.

Area of Science:

• Cardiovascular Biology
• Sepsis Pathophysiology
• Mitochondrial Function

Background:

• Sepsis-induced cardiomyopathy is a major cause of mortality.
• Prohibitin-1 (PHB1) links inflammation, metabolism, and oxidative stress.
• The role of circulating PHB1 in sepsis remains unknown.

Purpose of the Study:

• To investigate the functional role of intracellular and circulating PHB1 in sepsis-induced heart dysfunction.
• To elucidate the underlying mechanisms of PHB1's action in the heart during sepsis.

Main Methods:

• Utilized in vitro (HL-1 cardiomyocytes) and in vivo (rodent models) sepsis models.
• Investigated PHB1 translocation, secretion, and functional effects of recombinant PHB1.
• Assessed the involvement of Nuclear Factor (erythroid-derived 2)-like 2 (NFE2L2) and PI3K/AKT signaling pathways.

Main Results:

• Sepsis induced PHB1 translocation to the nucleus in cardiomyocytes and secretion from the liver, dependent on NFE2L2.
• Recombinant human PHB1 treatment protected cardiomyocytes from mitochondrial dysfunction and cytokine stress.
• PHB1 administration improved cardiac contractility and ATP production in septic mice, independent of NFE2L2 but partially dependent on PI3K/AKT.

Conclusions:

• PHB1 exhibits a novel cardioprotective role in sepsis.
• Circulating PHB1 acts as a pro-survival factor.
• PHB1 holds potential as a therapeutic agent or biomarker for sepsis and inflammatory disorders.