Transcriptional factor modulation by lipid peroxidation-derived aldehydes

Lipid aldehydes abundantly found in the nutritional and dietary fats, environmental pollutants, and endogenously generated in the body play a critical role in human health and diseases. The lipid aldehydes are very reactive and form conjugates with cellular glutathione, nucleic acids, and proteins and cause tissue dysfunction and damage. Unsaturated aldehydes, such as 4-hydroxynonenal and acrolein with their highly electrophilic functional groups, cause cytotoxic, genotoxic, and mutagenic effects. Further, lipid aldehydes deregulate normal functions of various protein kinases and phosphatases that lead to the activation/inactivation of various transcription factors responsible for transcribing various cytokines, chemokines, and growth factors involved in maintaining the cellular homeostasis. Specifically, lipid aldehydes regulate Nrf2-mediated antioxidative, NF-kB-mediated proinflammatory, AP1-mediated apoptotic, and E2F1-mediated cell-cycle pathways. This article briefly describes the significant role of lipid aldehydes in the regulation of various transcription factors with respect to their role in cell signaling and disease complications.