Enrique Cadenas, Ph.D.

Molecular Pharmacology and Toxicology

Oxidative Stress and the Cell Cycle


Enrique Cadenas is Professor at the Department of Molecular Pharmacology & Toxicology since 1992. His long-term research interests involve an interdisciplinary and comprehensive approach to the understanding of the molecular mechanisms underlying free radical toxicity under the broad umbrella of OXIDATIVE STRESS. The research areas developed in Enrique Cadenas' laboratory share the above general concept and are specifically defined as:

[a] ANTICANCER QUINONE TOXICITY AND PROGRESSION OF THE CELL CYCLE. These studies expand and advance ongoing research at the Principal Investigator's laboratory on the cellular and molecular mechanisms underlying the cytotoxicity of quinones. This research addresses efficient and controllable cytotoxic pathways for anticancer quinone metabolism elicited by reactive oxygen species. The research is centered on the effect of the latter on the uncontrolled cell growth characteristic of a tumor and, in particular, the role of the p21 gene on cell cycle arrest and inhibition of cell growth. The long-term goals within this area are to establish a relationship between reactive oxygen species formed during enzymic activation of quinones in cancer cells, induction of the p21 gene, and inhibition of cell proliferation through disruption of the cell cycle.

[b] BIOCHEMICAL TOXICOLOGY OF MYOGLOBIN OXIDATION STATES. Current interest in the mechanisms by which reactive oxygen species cause cellular injury in muscle has focused attention on the potential damaging role of the reaction between myoglobin and cellular peroxides. The oxidation of myoglobin within this reaction leads to a strong oxidant known as ferrylmyoglobin and it may be an early functional change during oxidative stress and, accordingly, it may play a critical role in the subsequent oxidation of muscle tissue. Research is conducted in order to evaluate the implication of these reactions for muscle oxidative injury associated with cardiomyopathies in general and ischemia/reperfusion injury in particular.

[c] MITOCHONDRIAL SOURCES OF OXYGEN RADICALS AND CELL FUNCTION IMPAIRMENT- This area focuses on the oxygen radical production at the inner mitochondrial membrane site (mitochondrial electron transfer chain) and at the outer mitochondrial membrane (monoamine oxidase activity) and the ensuing increase of the cellular and intramitochondrial steady-state concentration of oxygen radicals. Major emphasis is given to oxidative impairment of mitochondrial DNA and its consequences for mitochondrial function and cell senescence.

Selected Publications

  1. Cadenas, E. (1995) Mechanisms of oxygen activation and reactive oxygen species detoxification. In Oxidative-Induced Stress and Antioxidant Defenses in Biological Systems (Ahmad, S., Ed.), pp. 1-61, Chapman & Hall.
  2. Cadenas, E. (1995) Antioxidant and prooxidant functions of DT-diaphorase in quinone metabolism, Biochem. Pharmacol., 49, 127-140.
  3. Giulivi, C. and Cadenas, E. (1993) Formation of ferrylmyoglobin and its chemical reactivity towards electron-donating compounds. Methods Enzymol., 233, 189-202.
  4. Hauptmann, N., Grimsby, J., Shih, J.C., and Cadenas, E. (1996) The metabolism of tyramine by monoamine oxidase A/B causes oxidative damage to mitochondrial DNA. Arch. Biochem. Biophys.
  5. Qiu, X., Schönthal, A., Forman, H.J. and Cadenas, E. (1996) Induction of p21 in HCT116 cells by aziridinylbenzoquinones. A role for reactive oxygen species.