15-deoxy-Delta12,14-prostaglandin J2 as a potential endogenous regulator of redox-sensitive transcription factors.
15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)) has been known to display multifaceted cellular functions, including anti-inflammatory and cytoprotective effects. However, depending on the concentrations and intracellular microenvironment, this cyclopentenone prostaglandin can exert opposite effects. Because of the alpha,beta-unsaturated carbonyl moiety present in its cyclopentenone ring structure, 15d-PGJ(2) can act as a Michael reaction acceptor and readily interacts with critical cellular nucleophiles, such as cysteine thiol groups in proteins. Many of the biological effects induced by 15d-PGJ(2) involve redox-transcription factors as the potential targets. Thus, 15d-PGJ(2) can modulate the transcriptional activities of nuclear factor-kappaB (NF-kappaB), activator protein-1 (AP-1), nuclear factor-erythroid 2p45 (NF-E2)-related factors (Nrf2), hypoxia inducible factor (HIF), etc. 15d-PGJ(2) is also well known as an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARgamma). However, the regulation of the aforementioned redox-sensitive transcription factors by 15d-PGJ(2) is not necessarily mediated via PPARgamma activation, but rather involves covalent modification or oxidation of their critical cysteine residues acting as a redox-sensor. This commentary describes the biological and physiological functions of 15d-PGJ(2) and underlying biochemical and molecular mechanisms with emphasis on the modulation of redox-sensitive transcription factors and their regulators.
Kim
Eun-Hee
EH
National Research Laboratory of Molecular Carcinogenesis and Chemoprevention, College of Pharmacy, Seoul National University, Shinlim-dong, Kwanak-ku, Seoul 151-742, South Korea.
Surh
Young-Joon
YJ
D000818:Animals; D003545:Cysteine / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism*; D010084:Oxidation-Reduction; D047495:PPAR gamma / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D012926:Social Control, Formal; D014157:Transcription Factors / Q000378:metabolism*
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D047495:PPAR gamma; D014157:Transcription Factors; D003545:Cysteine; D015230:Prostaglandin D2