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Updated: Aug 16, 2026
Measurement of Heme Synthesis Levels in Mammalian Cells
Published on: July 9, 2015
Alpha-lipoic acid-induced heme oxygenase-1 expression is mediated by nuclear factor erythroid 2-related factor 2 and
Richard M Ogborne1, Stuart A Rushworth, Maria A O'Connell
1MRC Human Nutrition Research, Elsie Widdowson Laboratory, Cambridge, CB1 9NL, UK.
Objective:
Heme oxygenase-1 (HO-1), the rate-limiting enzyme in heme catabolism, plays a protective role in the vascular system. HO-1 induction inhibits cytokine production in macrophages. Antioxidants induce HO-1 expression in various cell types. Alpha-lipoic acid (ALA), a thiol-containing dietary antioxidant, exhibits protective effects in vascular disease and induces anti-inflammatory effects in monocytes. This study examined the effects of ALA on HO-1 expression in human monocytic cells.
Methods And Results:
ALA time and dose-dependently induced HO-1 mRNA expression in THP-1 cells, with peak expression at 4 hours and returning to baseline by 24 hours. This correlated with an increase in HO-1 protein expression. ALA stimulated translocation of the transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) into the nucleus and binding to a human HO-1 antioxidant response element (ARE) by 30 minutes. A dominant-negative Nrf2 inhibitor reduced ALA-induced HO-1 mRNA expression by 66%. Pretreatment with SB203580, a p38 mitogen-activated protein kinase inhibitor, reduced ALA-induced HO-1 mRNA expression by 75% and inhibited ALA-induced Nrf2 binding to the HO-1 ARE.
Conclusions:
These results demonstrate that ALA induces HO-1 expression in THP-1 monocytic cells via Nrf2 and p38. Further studies are required to investigate whether the protective effects of ALA in monocytes are mediated by HO-1.
