A decrease of ATP production steered by PEDF in cardiomyocytes with oxygen-glucose deprivation is associated with an...

Area of Science:

• Cardiovascular Science
• Cellular Biology
• Biochemistry

Background:

• AMP-activated protein kinase (AMPK) is a protective cardiovascular kinase during ischemia.
• AMPK inhibition shows neuroprotective effects in stroke.
• Pigment epithelium derived factor (PEDF) protects ischemic cardiomyocytes, but its role with AMPK is unclear.

Purpose of the Study:

• To investigate the relationship between PEDF and AMPK in cardiomyocytes under ischemic conditions.
• To elucidate the mechanism by which PEDF affects cardiomyocyte energy metabolism and survival.

Main Methods:

• Isolated rat neonatal and adult cardiomyocytes subjected to oxygen-glucose deprivation (OGD).
• Assessed AMPKα levels, ATP production, and ATP expenditure.
• Investigated the role of the PEDF/PEDFR/peroxisome proliferator activated receptor γ (PPARγ) axis and ubiquitin-dependent proteasomal degradation.

Main Results:

• PEDF reduced AMPKα levels, decreasing ATP production and expenditure, thereby increasing energy reserves and cell viability.
• Pharmacological AMPK inhibition reduced ATP production but not expenditure, leading to cell death.
• AMPKα degradation was mediated by a ubiquitin-dependent proteasomal pathway linked to the PEDF/PEDFR/PPARγ axis.
• Inhibition of PPARγ or proteasome blocked AMPKα degradation.

Conclusions:

• PEDF regulates cardiac ATP production via AMPKα and PPARγ.
• PEDF promotes AMPKα proteasomal degradation, reducing ATP production and expenditure.
• This mechanism enhances cardiomyocyte energy reserves and survival during OGD.