Ketone bodies upregulate endothelial connexin 43 (Cx43) gap junctions

Area of Science:

• * Veterinary Medicine
• * Animal Physiology
• * Molecular Biology

Background:

• * Ketosis is a metabolic disorder in lactating dairy cows resulting from negative energy balance post-calving.
• * Ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) accumulate in the blood and influence various physiological processes.
• * Previous research suggests ketone bodies affect endothelial cell function, including blood flow and immune responses.

Purpose of the Study:

• * To investigate the impact of ketone bodies (acetoacetate, beta-hydroxybutyrate, acetone) on connexin 43 (Cx43) expression and gap junctional intercellular coupling (GJIC) in bovine aortic endothelial cells (BAECs).

Main Methods:

• * Exposure of BAECs to individual and combined ketone bodies.
• * Confocal microscopy, Western blotting, and RT-PCR to assess Cx43 mRNA and protein levels.
• * Evaluation of GJIC and cell migration.
• * Analysis of ERK and p38 MAPK activation using specific inhibitors (PD98059, SB203580).

Main Results:

• * Ketone bodies significantly increased Cx43 mRNA and protein expression in BAECs.
• * Upregulation of GJIC and enhanced cell migration were observed following ketone body treatment.
• * Ketone bodies activated ERK and p38 MAPK pathways within 3 hours.
• * Inhibition of ERK and p38 MAPK antagonized the ketone-induced increase in Cx43 expression.

Conclusions:

• * Ketone bodies enhance Cx43 expression and GJIC in bovine aortic endothelial cells.
• * The signaling pathways involving ERK and p38 MAPK are crucial for mediating these effects.
• * Findings provide insights into the cellular mechanisms underlying ketosis in dairy cows.