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Cellular self-eating promotes pancreatitis
June 30, 2008To survive tough times, cells sometimes resort to a form of self-cannibalism called autophagy. But as Hashimoto et al. reveal, autophagy can have a down side, destroying the pancreas by prematurely activating a digestive enzyme.
In autophagy, a vesicle swallows a portion of cytoplasm and ferries it to the lysosome for digestion. The process is often beneficial, allowing hungry cells to recycle molecules, for example. However, the researchers previously discovered that in mice with pancreatitis the level of autophagy in pancreatic cells surges. Pancreatitis occurs when the enzyme trypsin dissolves cells from within. Normally, pancreatic cells fashion and discharge an inactive form of trypsin called trypsinogen, which remains inert until it reaches the small intestine. But if trypsinogen converts to trypsin before its release, it can damage or kill a pancreatic cell. Hashimoto et al. tested whether autophagy promotes this early activation by delivering trypsinogen to the lysosome, where enzymes turn it on.
The researchers gave mice injections of the compound cerulein, which spurs pancreatitis. Control animals suffered severe damage to the organ, which harbored numerous deteriorating cells. But rodents that lack a gene necessary for autophagy displayed almost no symptoms. To determine whether autophagy promotes trypsinogen activation, the team dosed pancreatic cells from both types of mice with cerulein. Cells from the autophagy-impaired animals carried much less activated trypsinogen than did cells from controls.
In rodents capable of autophagy, cerulein injections triggered much higher levels of trypsin activity in pancreatic tissue than did shots of saline, confirming that autophagy switches on the enzyme. The study is the first to reveal that autophagy can initiate a disease. The next step, the researchers say, is determining what triggers pancreatic cells to start eating themselves.
Rockefeller University Press
In rodents capable of autophagy, cerulein injections triggered much higher levels of trypsin activity in pancreatic tissue than did shots of saline, confirming that autophagy switches on the enzyme. The study is the first to reveal that autophagy can initiate a disease. The next step, the researchers say, is determining what triggers pancreatic cells to start eating themselves.
Rockefeller University Press
Autophagy Current Events and Autophagy News RSSInhibitor of heat shock protein is a potential anticancer drug, Penn study finds
Like yoga for office drones, cells do have coping strategies for stress. Heat, lack of nutrients, oxygen radicals - all can wreak havoc on the delicate internal components of a cell, potentially damaging it beyond repair.
HIV uses autophagy for its own means
Not satisfied with simply thwarting its host's defensive maneuvers, HIV actually twists one to its advantage, based on new findings from Kyei et al. in the July 27, 2009 issue of the Journal of Cell Biology (www.jcb.org). Vojo Deretic and colleagues suggest that autophagy-a stress response process-helps HIV to proliferate and that conversely, blocking autophagy lessens HIV production.
Waste disposal protein is mechanism behind cancer tumor suppression
"Taking out the trash" takes on a whole new meaning, as investigators at The Cancer Institute of New Jersey (CINJ) and Rutgers, The State University of New Jersey, have discovered that a waste disposal protein is the key to cancer tumor suppression in a process known as autophagy.
Scientists advance safety of nanotechnology
Scientists have identified for the first time a mechanism by which nanoparticles cause lung damage and have demonstrated that it can be combated by blocking the process involved, taking a step toward addressing the growing concerns over the safety of nanotechnology.
Muscle atrophy through thick but not thin
During desperate times, such as fasting, or muscle wasting that afflicts cancer or AIDS patients, the body cannibalizes itself, atrophying and breaking down skeletal muscle proteins to liberate amino acids.
Enhancing the effects of the drug used to treat chronic myeloid leukemia
Individuals with chronic myeloid leukemia (CML) are first treated with a drug known as imatinib mesylate. Although very effective, as the disease progresses it often becomes resistant to the drug.
Therapeutic effect of imatinib improved with addition of chloroquine
The therapeutic effects of the blockbuster leukemia drug imatinib may be enhanced when given along with a drug that inhibits a cell process called autophagy, researchers from the Kimmel Cancer Center at Jefferson reported in the Journal of Clinical Investigation.
TB breakthrough could lead to stronger vaccine
A breakthrough strategy to improve the effectiveness of the only tuberculosis vaccine approved for humans provided superior protection against the deadly disease in a pre-clinical test, report scientists at The University of Texas Health Science Center at Houston in Nature Medicine's Advance Online Publication March 1.
Self-digestion as a means of survival
In times of starvation, cells tighten their belts: they start to digest their own proteins and cellular organs. The process - known as autophagy - takes place in special organelles called autophagosomes.
Helicobacter pylori can multiply in autophagic vesicles
Helicobacter pylori, a Gram-negative, flagellated, microaerophilic bacterium, can selectively colonize in the human stomach. Its infection is widespread throughout the world, and is present in about 50% of the global human population with 80% in developing countries and 20-50% in industrialized countries.
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