PNPLA1 has a crucial role in skin barrier function by directing acylceramide biosynthesis.

Mutations in patatin-like phospholipase domain-containing 1 (PNPLA1) cause autosomal recessive congenital ichthyosis, but the mechanism involved remains unclear. Here we show that PNPLA1, an enzyme expressed in differentiated keratinocytes, plays a crucial role in the biosynthesis of ω-O-acylceramide, a lipid component essential for skin barrier. Global or keratinocyte-specific Pnpla1-deficient neonates die due to epidermal permeability barrier defects with severe transepidermal water loss, decreased intercellular lipid lamellae in the stratum corneum, and aberrant keratinocyte differentiation.

Synergistic effects of flavonoids and ascorbate on enhancement in DNA degradation induced by a bleomycin-Fe complex.

Flavonoids were examined for synergistic effects with ascorbate on enhancement of DNA degradation induced by a bleomycin(BLM)-Fe complex. The synergistic effects of flavonoids and ascorbate on DNA degradation induced by the BLM-Fe complex were observed to be greater with flavonoids such as isorhamnetin, kaempferol and morin, which accelerated oxidation more markedly in the presence, than in the absence of BLM. Conversely, myricetin and fisetin, which showed oxidation barely accelerated by the addition of BLM, inhibited DNA degradation promoted by ascorbate.

Oxidation of flavonoids which promote DNA degradation induced by bleomycin-Fe complex.

Sixteen flavonoids including quercetin and kaempferol and their relatives were examined for their ability to promote DNA degradation induced by the bleomycin (BLM)-Fe complex. Three hydroxyl groups in the flavonoidal nucleus were proposed as a crucial structural requirement for effectively promoting DNA degradation: 1). the C7-hydroxyl substitution in the A-ring; 2).