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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Basic-Leucine Zipper Transcription Factors, Chlorpromazine, Endocytosis, Fanconi Anemia Complementation Group Proteins, Gene Expression Regulation, Enzymologic, HEK293 Cells, Heme, Heme Oxygenase-1, Hemopexin, Humans, Metabolic Networks and Pathways, Mitochondria, Oxidative Stress, Respiration, Transcriptional Activation.
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Does hemopexin-dependent heme uptake via endocytosis regulate the Bach1 transcription repressor and heme oxygenase gene activation? Context: Intracellular heme plays versatile roles in a variety of physiological processes including mitochondrial respiration. Heme also induces the expression of genes such as heme oxygenase-1 (HO-1) by inactivating the transcription repressor Bach1 through direct binding. However, the source of heme for the regulation of the Bach1-HO-1 axis has been unclear. Considering that extracellular heme exists as a complex with hemopexin (Hx) in serum under the physiological conditions, heme-Hx complex may deliver heme for the gene regulation. Using a mammalian expression system, high secretory recombinant Hx (rHx) was developed. We examined the effects of rHx-bound heme on HO-1 expression and Bach1 in Hepa-1c1c7 liver cells and THP-1 macrophage cells. We investigated the uptake pathway of rHx-bound heme by treating cells with chlorpromazine (CPZ). rHx-bound heme induced the expression of HO-1 and decreased the level of Bach1 protein. CPZ inhibited the induction of the HO-1 expression by rHx-bound heme.
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rHx-bound heme was internalized into the cells via endocytosis, resulting in HO-1 expression and inactivation of Bach1. Final Decision: yes