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Professor of Biochemistry and Biophysics
Ph.D. University of Missouri 1970

The protein kinases mediate eukaryotic cells' response to internal and external stimuli such as a growth and differentiation factors, hormones, drugs and chemicals. The cell signaling pathways that transduce stimuli depend on cascades of phosphorylation /dephosphorylation events and kinase activities. The heme metabolic pathway, which converts, sequentially, heme to biliverdin plus CO, and bilirubin, reflects activities of heme oxygenase (HO) isozymes 1,2and 3, which constitute the HSP32 (heat shock/stress protein) family of proteins, and biliverdin reductase (BVR). Our recent studies have identified the heme metabolic pathway as a component of the cell signal transduction pathways. We have described CO as a signaling molecule; HO proteins as an intracellular "sink" for NO and potentially an intracellular oxygen sensor, bilirubin and biliverdin as modulators of protein phosphorylation. We have recently described biliverdin reductase as a new member of the dual specificity kinase (serine/threonine/tyrosine kinase) family, a leucine zipper-type transcription factor for cAMP and AP-1 regulated genes and an inhibitor of apoptosis. We are further investigating how the HO/BVR pathway modulates cell signaling and cell cycle processes.

Recent Publications

Lerner-Marmarosh N, Miralem T, Gibbs PE, Maines MD (2008) Human biliverdin reductase is an ERK activator; hBVR is an ERK nuclear transporter and is required for MAPK signaling. Proc Natl Acad Sci U S A, 105:6870-5

Tudor C, Lerner-Marmarosh N, Engelborghs Y, Gibbs PE, Maines MD (2008) Biliverdin reductase is a transporter of heme into the nucleus and is essential to regulation of HO-1 gene expression by hematin. Biochem J,

Maines MD, Miralem T, Lerner-Marmarosh N, Shen J, Gibbs PE (2007) Human biliverdin reductase, a previously unknown activator of protein kinase C betaII. J Biol Chem, 282:8110-22

Lerner-Marmarosh N, Miralem T, Gibbs PE, Maines MD (2007) Regulation of TNF-{alpha}-activated PKC-{zeta} signaling by the human biliverdin reductase: Identification of activating and inhibitory domains of the reductase. Faseb J,

Gibbs PE, Maines MD (2007) Biliverdin inhibits activation of NF-kappaB: Reversal of inhibition by human biliverdin reductase. Int J Cancer, 121:2567-74

Calabrese V, Butterfield DA, Scapagnini G, Stella AM, Maines MD (2006) Redox regulation of heat shock protein expression by signaling involving nitric oxide and carbon monoxide: relevance to brain aging, neurodegenerative disorders, and longevity. Antioxid Redox Signal, 8:444-77

Calabrese V, Maines MD (2006) Antiaging medicine: antioxidants and aging. Antioxid Redox Signal, 8:362-4

Ewing JF, Maines MD (2006) Regulation and expression of heme oxygenase enzymes in aged-rat brain: age related depression in HO-1 and HO-2 expression and altered stress-response. J Neural Transm, 113:439-54

Maines MD (2005) The heme oxygenase system: update 2005. Antioxid Redox Signal, 7:1761-6

Lerner-Marmarosh N, Shen J, Torno MD, Kravets A, Hu Z, Maines MD (2005) Human biliverdin reductase: a member of the insulin receptor substrate family with serine/threonine/tyrosine kinase activity. Proc Natl Acad Sci U S A, 102:7109-14

Maines MD, Gibbs PE (2005) 30 some years of heme oxygenase: from a "molecular wrecking ball" to a "mesmerizing" trigger of cellular events. Biochem Biophys Res Commun, 338:568-77

Maines MD (2005) New insights into biliverdin reductase functions: linking heme metabolism to cell signaling. Physiology (Bethesda), 20:382-9

Miralem T, Hu Z, Torno MD, Lelli KM, Maines MD (2005) Small interference RNA-mediated gene silencing of human biliverdin reductase, but not that of heme oxygenase-1, attenuates arsenite-mediated induction of the oxygenase and increases apoptosis in 293A kidney cells. J Biol Chem, 280:17084-92

Maines MD (2004) The heme oxygenase system: past, present, and future. Antioxid Redox Signal, 6:797-801

Kravets A, Hu Z, Miralem T, Torno MD, Maines MD (2004) Biliverdin reductase, a novel regulator for induction of activating transcription factor-2 and heme oxygenase-1. J Biol Chem, 279:19916-23

Mayer RD, Wang X, Maines MD (2003) Nitric oxide inhibitor N omega -nitro-l-arginine methyl ester potentiates induction of heme oxygenase-1 in kidney ischemia/reperfusion model: a novel mechanism for regulation of the oxygenase. J Pharmacol Exp Ther, 306:43-50

Maines MD (2003) Bile pigments: newcomers to the cell signaling arena. Toxicol Sci, 71:9-10

Wang X, Hauptmann N, Taylor E, Foreman M, Khawli LA, Maines MD (2003) Neotrofin increases heme oxygenase-1 selectively in neurons. Brain Res, 962:1-14

Graduate students in my laboratory work toward a Ph.D. degree in the following program[s]:

Ph.D. in Biochemistry

Ph.D. candidates in my laboratory may also be affiliated with these programs:

Contact Information

E-Mail: Mahin_Maines@urmc.rochester.edu

Mahin Maines
Department of Biochemistry and Biophysics
University of Rochester School of Medicine and Dentistry
601 Elmwood Ave, Box 712
Rochester, New York 14642

Office: Medical Center 5-8834
Telephone: (585) 275-5383; Fax: (585) 275-6007