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Investigate the timing and order of heme biosynthetic pathway enzyme activation during dimethylsulfoxide-induced erythroid differentiation in Friend leukemia virus-transformed cells.

February 1, 1976The Journal of Experimental MedicineOpen Access

Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells.

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Authors

SSShigeru SassaAlbert Einstein College of Medicine

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Implication

In vitro study demonstrates sequential induction of heme biosynthetic enzymes in mouse Friend leukemia cells, indicating step-by-step gene activation during erythroid differentiation.

Key Points

Investigate the timing and order of heme biosynthetic pathway enzyme activation during dimethylsulfoxide-induced erythroid differentiation in Friend leukemia virus-transformed cells.
Cultured mouse Friend leukemia virus-transformed T3-C1-2 cells with dimethylsulfoxide (DMSO) to induce erythroid differentiation.
Measured temporal activity changes of ALA synthetase, ALA dehydratase, uroporphyrinogen-I synthetase, ferrochelatase, and total heme concentration.
Assessed transcriptional dependence and early-phase sensitivity using actinomycin D and 5-bromo-2'-deoxyuridine (BrdU, 10⁻⁵ M) with or without thymidine (7 × 10⁻⁵ M) or uridine.
DMSO-treated cells exhibited a step-by-step increase in ALA synthetase, ALA dehydratase, uroporphyrinogen-I synthetase, ferrochelatase, and heme concentration across days 1, 1.5, 2, and 4, directly matching their order in the heme pathway.
Actinomycin D effectively blocked DMSO-mediated induction of all heme pathway enzymes, indicating that ongoing RNA transcription is necessary for differentiation.
BrdU selectively suppressed enzyme induction when present during the first 2 days of culture, and this inhibition was fully overcome by co-administration of thymidine but not uridine.

Cite This Study

Shigeru Sassa (1976) studied this question.

synapsesocial.com/papers/69ffa454581c6e761e77819d https://doi.org/10.1084/jem.143.2.305

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Implication

In vitro study demonstrates sequential induction of heme biosynthetic enzymes in mouse Friend leukemia cells, indicating step-by-step gene activation during erythroid differentiation.

Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells.

Discussion

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Implication

Key Points

Cite This Study

Sequential induction of heme pathway enzymes during erythroid differentiation of mouse Friend leukemia virus-infected cells.

Discussion

Member takes

Implication

Key Points

Cite This Study

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