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Plant Protein Mimics Hormone That Mitigates Diabetes and Obesity
Plant Protein Mimics Hormone That Mitigates Diabetes and Obesity -- Posted by Gumbo on 02-02-05 06:32
Plant Protein Mimics Hormone That Mitigates Diabetes and Obesity
Source: Purdue University
NEWSWISE Science News, 24-Jan-2005 --
A common protein that protects plants from fungal infection mimics the
activity of a hormone in mammals that is linked to weight loss and is
believed to play a role in mitigating heart disease, obesity and diabetes,
according to a team of researchers at Purdue University and several
collaborating institutions.
The research has the potential to lead to a simple screening system for
developing new drugs to treat these and several other human diseases,
including some forms of cancer, said Ray Bressan, distinguished professor of
horticulture and one of the study's authors.
The study also raises questions about the human health role of this type of
plant protein, found in many fruits, seeds and vegetables such as grapes,
oats and tomatoes.
The protein, called osmotin, belongs to a large, diverse family of proteins
that defend plants from fungal pathogens. Bressan and his colleagues report
in the current issue (Friday, Jan. 21) of Molecular Cell that a protein in
mammal muscle cells called a receptor, which normally binds to the hormone
adiponectin, also binds osmotin.
They also found that the plant-derived osmotin activates the receptors in
mammals in the same manner as adiponectin.
"We've found that this plant protein mimics the behavior of adiponectin in
muscle cells," Bressan said. "It's very possible that the plant protein
could play a role in the prevention of diseases like diabetes as well,
because it has the same target as adiponectin in mammal cells - the
adiponectin receptor."
The binding of hormones and other proteins to receptors activates specific
responses. For example, when the hormone oxytocin binds to cells in the
uterus, contractions - and childbirth - begin.
When bound to its receptor, adiponectin regulates sugar uptake and, in mouse
models, prevents the development of diabetes and atherosclerosis, or the
hardening of the arteries associated with heart disease. Previous studies
have shown that people with diabetes tend to have lower levels of
adiponectin in their blood than non-diabetics. In addition, adiponectin
levels tend to be lower in the obese and in patients with heart disease than
in healthier individuals.
Whether the beneficial effects of adiponectin can be induced by osmotin is
currently unknown.
"We've shown the connection between adiponectin and the plant protein
osmotin," Bressan said. "That connection is that the same protein in animal
cells recognizes both osmotin and adiponectin and responds to them in the
same way. There's an inference that the plant protein very possibly could
have a similar protective connection to those diseases, but we don't yet
know that."
In the current study, researchers looked at how osmotin functions in yeast,
a fungus often used as a model organism in molecular and biochemical
experiments. They also assessed how osmotin acts in adiponectin receptors in
a culture of mouse muscle cells.
The yeast system they developed hints at the possibility of using yeast to
screen for new pharmaceutical products to target diabetes, heart disease and
obesity, Bressan said. Running a screen in yeast is a highly efficient first
step in looking for potentially therapeutic agents because yeast is easy to
grow and is very well understood at the cellular and molecular genetic
levels.
"It may be possible to expose different drug candidates to the receptor in
yeast that recognizes osmotin and see which compounds activate this
receptor," he said. "Another approach would be to take the gene for the
animal receptor, insert it into yeast, and start asking those same
questions - what other compounds does the receptor recognize?"
In their study, the researchers determined that activation of the osmotin
receptor in yeast kills yeast cells by inducing a phenomenon called
"apoptosis," or programmed cell death. Thus, a screen to look for compounds
that activate this receptor could simply rely on finding out which compounds
kill yeast cells by the same process.
This study also shows that we need to look more closely at the way our
bodies use the foods we eat, especially plant-based foods such as fruits,
nuts and vegetables.
"Proteins like osmotin are consumed by people all the time," Bressan said.
"Yet no studies have been done to determine how the presence or absence of
these proteins in the diet affects us."
Osmotin is a stable protein that is resistant to heat, acidity and enzymes,
meaning it could circulate through the body without being broken down by
digestion, he said.
Whether osmotin plays any role in the health benefits attributed to diets
high in fruits and vegetables is a tantalizing possibility, and this
research opens the door to that question, Bressan said.
"We know that osmotin is an active protein in many of the plants we eat," he
said. "We control and label nutrients like fats, carbohydrates and protein -
but the really active materials in the foods we eat are the ones we know the
least about and don't label in our foods."
Both adiponectin and osmotin jump-start a process called "AMP kinase
phosphorylation," which increases both sugar and fat use by muscle cells.
"By binding to the adiponectin receptor, osmotin, like adiponectin, can
control the energy status of muscle cells, " said Meena Narsimhan, research
scientist at Purdue's Bindley Bioscience Center and a study co-author.
Curiously, adiponectin also can kill some types of mammalian cells,
Narsimhan said.
"Other research has shown a strong correlation between low levels of
adiponectin and increased risk of breast cancer," she said.
Whether osmotin also has a similarly lethal effect on any types of mammalian
cells remains to be seen; however, osmotin, when bound to its receptor on
yeast cells, does kill those cells, Narsimhan said.
"What's interesting about this research is that is raises so many
questions," she said.
Collaborating researchers in this study include Maria A. Coca, who first
isolated the yeast receptor gene, at the Instituto de Biologia Molecular,
Barcelona, Spain; Dae-Jin Yun of the Environmental Biotechnology National
Core Research Center at Gyeongsang National University, Korea; Jingo Jin,
Barbara Damsz and Paul Hasegawa at Purdue's Center for Plant Environmental
Stress Physiology; Toshimasa Yamauchi, Yusuke Ito and Takashi Kadowaki at
the University of Tokyo Graduate School of Medicine and CREST, Japan Society
and Technology Corporation; Jose Pardo with the Instituto de Recuersos
Naturales y Agrobioloia in Seville, Spain; and Kyeong Kyu Kim with the
Sungkyunkwan University School of Medicine, Suwon, Korea.
Funding was provided by the National Science Foundation, the Korean Ministry
of Science and Technology, the Program for Promotion of Fundamental Studies
in Health Sciences of the Organization for Pharmaceutical Safety and
Research of Japan, and the Korea Science and Engineering Foundation
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