Areas of Interest
Dr. Jansson has two main areas of interest. Her major studies
are on the cytochrome P450 (CYP)-containing monooxygenases
responsible for drug, chemical and steroid oxidation. She has
developed a heterologous expression system in Escherichia coli
for the production of the different membranous forms of
cytochrome P450 (Jansson, et al., "Enhanced expression of CYP1B1
in E. coli." Toxicology 144:211-219, 2000). She has also
developed conditions for purification of these proteins and
reconstitution systems to incorporated them into synthetic
phospholipid vesicles with the reductase, NADPH-cytochrome P450
reductase in order to examine their monooxygenase
characteristics. She applied her system to the study of
involvement of CYP1B1 mutations in Primary Congenital Glaucoma (PCG),
and was able to provide a possible explanation for the
incomplete penetration in the disease phenotype of individuals
with two different mutations in this hemoprotein. It had been
shown that individuals with deletion genotypes of CYP1B1
developed PCG. In families with this disease individuals
homozygous for the defective gene develop PCG. At least 26
mutations are known. A proportion of individuals homozygous for
some of these point mutations did not develop PCG (incomplete
penetrance). Dr. Jansson was able to show that two mutations,
each resulting in a single amino acid substitution of CYP1B1,
G61E and R469W, resulted in monooxygenases with considerably
diminished activities (Jansson, et al.,"Effect of two mutations
of human CYP1B1, G61E and R469W, on stability and endogenous
steroid substrate metabolism." Pharmacogenetics 11:1-9 2001).
She suggested that environmental factors could, in certain
instances, cause elevations in the levels of these inducible
enzymes, thus compensating for their diminished activities. This
compensation might thus permit normal eye development.
A second area of Dr. Janssons studies have included
examination of protein-protein interaction between cytochrome
P450 forms and another membrane hemoprotein, cytochrome b5. She
has examined the nature of the charge pairing interaction
between cytochrome b5 and P450, and the topography of the
enzymes within the endoplasmic reticulum membrane. Normally in a
tissue, such as liver, there are at least a dozen different
forms of cytochrome P450 present. Cytochrome b5 can interact
with a number of these forms. What determines whether such
interaction occurs? Dr. Jansson was able to show that substrate
is what stimulates this interaction (Jansson & Schenkman,
"Substrate influence on interaction between cytochrome P450 and
cytochrome b5." Archives of Biochemistry and Biophysics
325:265-269, 1996). In further collaboration with Dr.Schenkman
she was able to show the interaction was due to a charge-pairing
involving basic residues on the proximal surface of cytochrome
P450 and acidic residues around the heme edge of cytochrome b5 (Schenkman,
et al., "Charge-dependent sidedness of cytochrome p450 forms
studied by quartz crystal microbalance and atomic force
microscopy." Archives of Biochemistry and Biophysics 385:78-87,
2001). In a recent review current understanding of the
interactions between these hemoproteins in the monooxygenase
reaction is discussed (Schenkman & Jansson, "The many roles of
cytochrome b5" Pharmacology & Therapeutics 97:139-152, 2003).
Publications
Selected Publications
Choudhary D, Jansson I, Schenkman JB, Sarfarazi M, Stoilov I.
Comparative expression profiling of 40 mouse cytochrome P450
genes in embryonic and adult tissues. Arch Biochem Biophys. 2003
Jun 1;414(1):91-100.
Estavillo C, Lu Z, Jansson I, Schenkman JB, Rusling JF.
Epoxidation of styrene by human cyt P450 1A2 by thin film
electrolysis andperoxide activation compared to solution
reactions.
Biophys Chem. 2003 May 1;104(1):291-6.
Schenkman JB, Jansson I. The many roles of cytochrome b5.
Pharmacol Ther. 2003 Feb;97(2):139-52. Review.
Bengtsson M, Danielsson F, Jansson IE, Johansson U.
Identification of a new HLA-DPB1 allele,HLA-DPB1*9001. Tissue
Antigens. 2002 Apr;59(4):344-6.
Hanas R, Adolfsson P, Elfvin-Akesson K, Hammaren L, Ilvered
R, Jansson I, Johansson C, Kroon M, Lindgren J, Lindh A,
Ludvigsson J, Sigstrom L, Wiik A, Aman J, Jansson I, Wilk A.
Indwelling catheters used from the onset of diabetes decrease
injection pain and pre-injection anxiety. J Pediatr. 2002
Mar;140(3):315-20. Erratum in: J Pediatr 2002 Aug;141(2):298.
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