Our laboratory is addressing two of the most important issues in vascular biology today: stroke mechanisms; and irreversible cellular destruction in the cardiovascular system caused by alcohol and substance abuse. These studies have already led to the prevention of atherosclerotic lesions, hypertension and stroke-like events in experimental animal models. Additional experimental studies, using manipulations in divalent cation metabolism, have been very effective in the prevention and amelioration of alcohol-, phencyclidine-, cocaine-, and other substance abuse-induced strokes.
We are using intact animals, isolated organs, tissues and cells in culture to understand how divalent cations (Mg2+ and Ca2+), sphingolipids, lipid messengers, protein kinase C and nuclear transcription factors control normal fuctions of vascular smooth muscle cells, cardiac myocytes and several types of neuronal cells. In order to accomplish these goals, we employ various state-of-the-art techniques: NMR spectroscopy; in-vivo high-resolution TV microscopy; digital image microscopy; confocal laser scanning microscopy; culture of primary cells; Mg2+ ion-selective electrodes; mono- and polyclonal antibodies; antisense oligonucleotides; and lipid chemistry. Use of the various models and techniques has led us to hypothesize that magnesium ions can regulate voltage-, receptor-, and leak-operated membrane channels in a number of cell types and that various cellular signaling pathways, particularly isoforms of PKC and sphingolipids are turned on or off by the actions and concentrations of Mg2+ at multiple cellular sites.
Li, M., Zheng, T., Wang J., Altura, B. T., and Altura, B. M. (1999). Extracellular magnesium regulates effects of vitamin B6, B12 and folate on homocysteinemia-induced depletion of intracellular magnesium ions in canine cerebral smooth muscle cells: possible relationship to [ Ca2+]i, atherogenesis and stroke. Neurosci. Lett. 274, 83-86.
Li, W., Zheng, T., Wang, J., Altura, B. T., and Altura, B. M. (1999). Pyrrolidine dethiocarbamate prevents ethanol-induced elevation of [Ca2+]i in cultured canine carebral vacsular smooth muscle cells. Neurosci. Lett. 266, 205-208.
Yang, Z. W., Wang, J., Zheng, T., Altura, B. T., and Altura, B. M. (2000). Low [Mg2+]o, induces contraction of cerebral arteries: roles of tyrosine and mitogen-activated protein kinases. Am. J. Physiol. Heart Circ. Physiol. 279, H185-H194.
Yang, Z. W., Gebrewold, A., Nowakowski, M., Altura, B. T., and Altura, B. M. (2000). Mg2+-induced endothelium-dependent relaxation of blood vessels and blood pressure lowering: role of NO. Am. J. Physiol. Regulatory Integrative Comp. Physiol. 278, R628-R639.
Zheng, T., Li, W., S., Wang, J., Altura, B. T., and Altura, B. M. (2000). Sphingomyelinase and ceramide analogs induce contraction and rises in [Ca2+]i in canine cerebral vascular muscle. Am. J. Physiol. Heart Circ. Physiol. 278, H1421-H1428.
Wenyan Li, Ph.D., Research Associate
Zhi-wei Yang, M.D., Ph.D., Research Associate
Ad Hoc Reviewer, NIH, NSF, and USDA study sections
Reviewer for various journals and funding organizations