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Faculty
Ingela
Jansson
Assistant Professor of Cell Biology
ijansson@neuron.uchc.edu
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).
Laboratory Home Page
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. |