Lactic acid induces HSPA1A expression through ERK1/2 activation

Area of Science:

• Biochemistry
• Cell Biology
• Molecular Biology

Background:

• Heat shock protein (HSP) A1A plays a crucial role in cellular protection against various stressors.
• Traditional Japanese rice black vinegar, Kurozu, is known for its potential health benefits.
• Understanding the molecular mechanisms behind HSP induction is vital for developing cellular protection strategies.

Purpose of the Study:

• To investigate the effect of concentrated Kurozu and its components on HSPA1A expression in normal rat liver RLN-10 cells.
• To elucidate the signaling pathways involved in lactic acid-induced HSPA1A expression.
• To explore the role of G protein-coupled receptor 81 (GPR81) in HSPA1A induction.

Main Methods:

• Treatment of RLN-10 cells with concentrated Kurozu, lactic acid, and 3,5-dihydroxybenzoic acid (DHBA).
• Assessment of HSPA1A expression levels.
• Inhibition studies using staurosporine and a selective MEK1/2 inhibitor (SL327).
• Analysis of ERK1/2 phosphorylation.

Main Results:

• Concentrated Kurozu and lactic acid significantly increased HSPA1A expression in a concentration-dependent manner.
• Lactic acid induction of HSPA1A was inhibited by staurosporine and SL327, suggesting involvement of the MEK/ERK pathway.
• Lactic acid treatment led to increased phosphorylation of ERK1/2.
• DHBA also induced HSPA1A expression, notably at lower concentrations than lactic acid, potentially due to higher affinity for GPR81.

Conclusions:

• Lactic acid, a key component of Kurozu, induces HSPA1A expression through the activation of the ERK1/2 signaling pathway.
• DHBA, acting as a GPR81 ligand, also upregulates HSPA1A, indicating a potential role for GPR81 in this process.
• These findings provide insights into the molecular mechanisms underlying the protective effects of Kurozu components on cells.