Andrea Romani, MD, PhD

Associate Professor View Curriculum Vitae (pdf) E528 10900 Euclid Ave Cleveland, OH 44116-4970 Phone: 216-368-1625 Fax: 216-368-5586 andrea.romani@case.edu

Mammalian cells tightly control cellular magnesium content by partitioning Mg2+ within cellular compartments and by transporting it across the plasma membrane. Under resting conditions, Mg2+ is evenly compartmentalized within mitochondria, nucleus and endo-sarco-plasmic reticulum (~16-18 mM within each of these compartments). An additional pool of Mg2+ is present in the cytoplasm, mostly in the form of a complex with ATP or other phospho-nucleotides (~5 mM). As a result of this partitioning/complexing, less than 1 mM is present as free [Mg2+] in the cytoplasm or within the mitochondria matrix.

The administration of adrenergic agonists to cardiac or liver cells markedly enhances Mg2+ extrusion via a cAMP-activated Na+-dependent process. Hormones that counteract adren-ceptor stimulation (e.g. vasopressin or insulin) prevent Mg2+ extrusion and/or promote the accumulation of a significant amount of Mg2+ within these cell types via protein kinase C signaling.

The ability of cardiac or liver cells to accumulate is specifically inhibited under pathological conditions such as diabetes (both type-I and type-II) or chronic alcohol consumption. Magnesium extrusion is also altered under these pathological conditions. In addition, both diabetes and alcohol consumption result in a marked decrease of cellular ATP level and cytoplasmic Mg2+ content.

The long term goal of my lab are: 1) to understand how cardiac and liver cells regulate Mg2+ transport and homeostasis under physiological conditions, and how these mechanisms are altered under diabetic conditions or following prolonged alcohol consumption, 2) to identify proteins specifically modified under diabetic conditions and following chronic alcohol consumption which affect Mg2+ homeostasis and transport, and 3) the short- and long-term implications of changes in cellular Mg2+ content for the operation of specific enzymes located within the mitochondria and the endo-sarco-plasmic reticulum.

• Sugimoto J, Romani AM, Valentin-Torres AM, Luciano AA, Kitchen CMR, Funderburg N, Mesiano S, Bernstein HE (2012) Magnesium sulfate decreases inflammatory cytokine production: A novel innate immuno-modulatory mechanism. Journal of Immunology, 188: 6338-6346. PMID: 22611240
• Harper-Jacob, A, Crumbly A, Romani A (2012) Acute effect of ethanol on hepatic reticular G6Pase and Ca²⁺ pool. Alcoholism: Clinical and Experimental Research, in press.
• Romani A (2012) Cellular Magnesium Homeostasis in mammalian cells, in Metal Ions in Life Science: Metallomics and the Cell, vol 12 (Banci L, ed.), Sigel A, Sigel H, and Sigel RKO series Eds. Basel, Switzerland.
• DiNuoscio G, Romani A (2012) Tissue magnesium homeostasis and ethanol administration, in ‘Progress in Alcohol liver Disease’ (Romani A. ed.), Research-Post Publishing Co. (to be published in Fall 2012)