Dr. Vittorio Calabrese, M.D., Ph.D.

ASSOCIATE PROFESSOR OF CLINICAL BIOCHEMISTRY
Biochemistry & Mol. Biology Section, Department of Chemistry, Faculty of Medicine, University of Catania.
Viale Andrea Doria, 6. 95125 - Catania- Italy

Degrees:
4/9/1984 Graduation in Medicine, with magna cum laude, University of Catania (Italy). Thesis: Modifications of brain lipid metabolism during aging
7/8/1988 Degree of specialist in Neurology, with magna cum laude, University of Catania (Italy). Thesis: Oxidative stress in central nervous system.
4/8/1996 Assistant Professor in Biochemistry, Department of Biochenmistry, University of Catania.

Awards:
1987 Post-Doctoral fellow in Neurobiology at the New York University Medical School, (N.Y.), Department of Pharmacology:“Neurodegenerative disorders: the role played by endotoxins and xenobiotics”
1989 Post-Doctoral fellow in Neuropharmacology at the Thomas Jefferson University Medical School (Philadelphia, PA,) Department of Pharmacology: “Oxidative stress and energy transduction defects in Neurodegenerative disorders”.
2000-2003:
Visiting Professor University College London, Department of Neurochemistry, funded by Wellcome Trust of a Grant on “The role of antioxidants in L-DOPA induced damage to the Substantia Nigra”.
Visiting Professor Northwick Park Institute for Medical Research, Department of Surgical Research, University of London, Research Program on “The role of heat shock signal and heme oxygenase on neuroprotection”.
Visiting Professor University of Kentucky, Department of Chemistry, Research Program on “Nutritional antioxidants and cellular stress response in Neuroscience”.
Visiting Professor Blanchette Rockefeller Neuroscience Institute, West Virginia University (MD), Program on “Functional Genomic in Aging, Neurodegenerative Disorders and Longevity”.
Coordinator Mediterranean-Europian Academy of Antiaging Medicine

Membership of Scientific Society:

  • S.I.B. Italian Society of Biochemistry.
  • S.I.B.S Italian Society of Experimental Biology.
  • SIBIOC Italian Society of Clinical Biochemistry
  • ISN International Society of Neurochemistry
  • ESN European Society of Neurochemistry
  • A4M American Academy Antiaging Medicine

Areas of Interest

  1. Role of Oxidative Stress and Mitochondrial dysfunction in Aging, Neurodegenerative disorders and Longevity
  2. Nutritional Antioxidants and Modulation of cellular redox state.
  3. Heat shock signal pathway and brain cell stress response
  4. Alcohol metabolism and alcohol-related pathology
  5. Gasobiology of the CNS: Role of Nitric Oxide (NO), Carbon Monoxide (CO) and Hydrogen sulfite (H2S) in the regulation of gene expression
  6. Carbon monoxide and organ transplantation

ABSTRACT

REDOX REGULATION OF CELLULAR STRESS RESPONSE IN
AGING BRAIN AND LONGEVITY: ROLE OF VITAGENES

Oxidative damage plays a crucial role in the brain aging process and induction of heat shock protein (HSPs) is critically utilized by brain cells in the repair process following various pathogenic insults. This basic information has been exploited to develop novel strategies in clinical therapeutics. Perturbation of cellular oxidant / antioxidant balance has been claimed to be involved in the neuropathogenesis of several disease states, including stroke, Parkinson’s disease, Alzheimer’s disease and physiological aging1. However, in contrast to the conventional idea that reactive species mostly serve as a trigger for oxidative damage of biological structures, we now know that low physiologically relevant concentration of reactive oxygen species can regulate a variety of key molecular mechanisms. Oxidative stress, in fact, hqas been demonstrated to modulate the expression and activity of important antioxidant enzymes as well as to enhance expression and/or DNA binding of numerous transcription factors, including fos, SAPK, NFkB and HSF (heat shock factor)2. HSF is the transcriptional activator for the synthesis of cytoprotective proteins called heat shock proteins (HSPs). HSPs induction is not only a signal for detection of physiological stress, but is utilized by the cells in the repair process following a wide range of injuries3. Cells constitutively overexpressing HSPs are resistant to a variety of oxidants and to heat shock, and it has been suggested that the protective effect against oxidative injury may result from protection against oxidant-induced DNA damage4. In addition, an increasing body of evidence suggests that dysfunction of cell energy metabolism is an important factor in NO-mediated neurotoxicity and that the intracellular content of thiols is crucial in determining the sensitivity of cells to oxidative and nitrosative stress5. Recently, the involvement of the heme oxygenase (HO) pathway in antidegenerative mechanisms has received considerable attention, as it has been demonstrated that the expression of HO is closely related to that of amyloid precursor protein (APP). HO induction, which occurs togheter with the induction of other HSPs during various physiophatological conditions6, by generating the vasoactive molecule carbon monoxide and the potent antioxidant bilirubin could represent a protective system potentially active against brain oxidative injury7-10.
We have recently focused our recent research on the role of carnitine system in cellular stress tolerance and antidegeneration. In the present study we investigated, in rats 6, 12 and 28 months old, and in rats 28 months old receiving for 6 months 1g/Kg/die acetylcarnitine (LAC), the role of heat shock signals on aging-induced changes in mitochondrial bioenergetics and antioxidant status. In all brain regions examined mRNA and protein synthesis of Hsp70 and Hsp60 increased with age up to 28 months; at this age the maximum induction was observed in the hippocampus and substantia nigra followed by cerebellum, cortex, and striatum. Hsps induction was associated with significant changes in glutathione (GSH) redox state and HNE levels. Interestingly, a significant positive correlation between decrease in GSH/GSSG ratio and increase in Hsp70 was observed in all brain regions examined during aging. Analysis of mitochondrial complexes showed a progressive decrease in Complex I activity and protein synthesis in all brain regions examined and this was associated with up-regulation of mRNA complex subunit expression. Interestingly, treatment with LAC resulted in a marked decrease in HNE and DPNH content associated with increased protein expression and activity of the heat shock protein (Hsp 32, HO-1) heme oxygenase-1, primarily in the hippocampus, cortex and cerebellum. Our results sustain a role for GSH redox state in Hsp expression. In particulaR, increase of heme oxygenase expression promotes the functional recovery of oxidatively damaged proteins and protects cells from progressive age-related cell damage. Conceivably, therapeutic strategies focussing on acetylcarnitine treatment, by up-regulating HO signal pathway and thus increasing bilirubin levels, may represent a crucial mechanism of defence against free radical-induced damage occurring in aging brain and in neurodegenerative disorders.


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