Pegasus Biochemistry Research Institute
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Immune System
The immune system, which is made up of special cells, proteins, tissues, and organs, defends people against germs and microorganisms every day. In most cases, the immune system does a great job of keeping people healthy and preventing infections. But sometimes problems with the immune system can lead to illness and infection.
About the Immune System
The immune system is the body's defense against infectious organisms and other invaders. Through a series of steps called the immune response, the immune system attacks organisms and substances that invade body systems and cause disease.
The immune system is made up of a network of cells, tissues, and organs that work together to protect the body. The cells involved are white blood cells, or leukocytes, which come in two basic types that combine to seek out and destroy disease-causing organisms or substances.
Leukocytes are produced or stored in many locations in the body, including the thymus, spleen, and bone marrow. For this reason, they're called the lymphoid organs. There are also clumps of lymphoid tissue throughout the body, primarily as lymph nodes, that house the leukocytes.
The leukocytes circulate through the body between the organs and nodes via lymphatic vessels and blood vessels. In this way, the immune system works in a coordinated manner to monitor the body for germs or substances that might cause problems.
The two basic types of leukocytes are:
1. phagocytes, cells that chew up invading organisms
2. lymphocytes, cells that allow the body to remember and recognize previous invaders and help the body destroy them
A number of different cells are considered phagocytes. The most common type is the neutrophil, which primarily fights bacteria. If doctors are worried about a bacterial infection, they might order a blood test to see if a patient has an increased number of neutrophils triggered by the infection. Other types of phagocytes have their own jobs to make sure that the body responds appropriately to a specific type of invader.
The two kinds of lymphocytes are B lymphocytes and T lymphocytes. Lymphocytes start out in the bone marrow and either stay there and mature into B cells, or they leave for the thymus gland, where they mature into T cells. B lymphocytes and T lymphocytes have separate functions: B lymphocytes are like the body's military intelligence system, seeking out their targets and sending defenses to lock onto them. T cells are like the soldiers, destroying the invaders that the intelligence system has identified.
Here's how it works:
When antigens (foreign substances that invade the body) are detected, several types of cells work together to recognize them and respond. These cells trigger the B lymphocytes to produce antibodies, specialized proteins that lock onto specific antigens.
Once produced, these antibodies continue to exist in a person's body, so that if the same antigen is presented to the immune system again, the antibodies are already there to do their job. So if someone gets sick with a certain disease, like chickenpox, that person typically doesn't get sick from it again.
This is also how immunizations prevent certain diseases. An immunization introduces the body to an antigen in a way that doesn't make someone sick, but does allow the body to produce antibodies that will then protect the person from future attack by the germ or substance that produces that particular disease.
Although antibodies can recognize an antigen and lock onto it, they are not capable of destroying it without help. That's the job of the T cells, which are part of the system that destroys antigens that have been tagged by antibodies or cells that have been infected or somehow changed. (Some T cells are actually called "killer cells.") T cells also are involved in helping signal other cells (like phagocytes) to do their jobs.
Antibodies also can neutralize toxins (poisonous or damaging substances) produced by different organisms. Lastly, antibodies can activate a group of proteins called complement that are also part of the immune system. Complement assists in killing bacteria, viruses, or infected cells.
All of these specialized cells and parts of the immune system offer the body protection against disease.
This protection is called immunity.
Immunity
Humans have three types of immunity — innate, adaptive, and passive:
Innate Immunity
Everyone is born with innate (or natural) immunity, a type of general protection. Many of the germs that affect other species don't harm us. For example, the viruses that cause leukemia in cats or distemper in dogs don't affect humans. Innate immunity works both ways because some viruses that make humans ill — such as the virus that causes HIV/AIDS — don't make cats or dogs sick.
Innate immunity also includes the external barriers of the body, like the skin and mucous membranes (like those that line the nose, throat, and gastrointestinal tract), which are the first line of defense in preventing diseases from entering the body. If this outer defensive wall is broken (as through a cut), the skin attempts to heal the break quickly and special immune cells on the skin attack invading germs.
Adaptive Immunity
The second kind of protection is adaptive (or active) immunity, which develops throughout our lives. Adaptive immunity involves the lymphocytes and develops as people are exposed to diseases or immunized against diseases through vaccination.
Passive Immunity
Passive immunity is "borrowed" from another source and it lasts for a short time. For example, antibodies in a mother's breast milk provide a baby with temporary immunity to diseases the mother has been exposed to. This can help protect the baby against infection during the early years of childhood.
Everyone's immune system is different. Some people never seem to get infections, whereas others seem to be sick all the time. As people get older, they usually become immune to more germs as the immune system comes into contact with more and more of them. That's why adults and teens tend to get fewer colds than kids — their bodies have learned to recognize and immediately attack many of the viruses that cause colds.
Problems of the Immune System
Disorders of the immune system fall into into four main categories:
1. immunodeficiency disorders (primary or acquired)
2. autoimmune disorders (in which the body's own immune system attacks its own tissue as foreign matter)
3. allergic disorders (in which the immune system overreacts in response to an antigen)
4. cancers of the immune system
Immunodeficiency Disorders
Immunodeficiencies occur when a part of the immune system is not present or is not working properly. Sometimes a person is born with an immunodeficiency (known as primary immunodeficiencies), although symptoms of the disorder might not appear until later in life. Immunodeficiencies also can be acquired through infection or produced by drugs (these are sometimes called secondary immunodeficiencies).
Immunodeficiencies can affect B lymphocytes, T lymphocytes, or phagocytes. Examples of primary immunodeficiencies that can affect kids and teens are:
IgA deficiency is the most common immunodeficiency disorder. IgA is an immunoglobulin that is found
primarily in the saliva and other body fluids that help guard the entrances to the body. IgA deficiency is a disorder in which
the body doesn't produce enough of the antibody IgA. People with IgA deficiency tend to have allergies or get more colds and
other respiratory infections, but the condition is usually not severe.
Severe combined immunodeficiency (SCID) is also known as the "bubble boy disease" after a Texas
boy with SCID who lived in a germ-free plastic bubble. SCID is a serious immune system disorder that occurs because of a lack
of both B and T lymphocytes, which makes it almost impossible to fight infections.
DiGeorge syndrome (thymic dysplasia), a birth defect in which kids are born without a thymus gland, is
an example of a primary T-lymphocyte disease. The thymus gland is where T lymphocytes normally mature.
Chediak-Higashi syndrome and chronic granulomatous disease both involve the inability
of the neutrophils to function normally as phagocytes.
Acquired (or secondary) immunodeficiencies usually develop after someone has a disease, although they can also be the result of malnutrition, burns, or other medical problems. Certain medicines also can cause problems with the functioning of the immune system.
Acquired (secondary) immunodeficiencies include:
HIV (human immunodeficiency virus) infection/AIDS (acquired immunodeficiency
syndrome) is a disease that
slowly and steadily destroys the immune system. It is caused by HIV, a virus that wipes out certain types of lymphocytes called
T-helper cells. Without T-helper cells, the immune system is unable to defend the body against normally harmless organisms,
which can cause life-threatening infections in people who have AIDS. Newborns can get HIV infection from their mothers while
in the uterus, during the birth process, or during breastfeeding. People can get HIV infection by having unprotected sexual
intercourse with an infected person or from sharing contaminated needles for drugs, steroids, or tattoos.
Immunodeficiencies caused by medications. Some medicines suppress the immune system. One of the drawbacks of
chemotherapy treatment for cancer, for example, is that it not only attacks cancer cells, but other fast-growing, healthy
cells, including those found in the bone marrow and other parts of the immune system. In addition, people with autoimmune
disorders or who have had organ transplants may need to take immunosuppressant medications, which also can reduce the immune
system's ability to fight infections and can cause secondary immunodeficiency.
Autoimmune Disorders
In autoimmune disorders, the immune system mistakenly attacks the body's healthy organs and tissues as though they were foreign invaders. Autoimmune diseases include:
Lupus, a chronic disease marked by muscle and joint pain and inflammation (the abnormal immune response also may
involve attacks on the kidneys and other organs.)
Juvenile rheumatoid arthritis, a disease in which the body's immune system acts as though certain
body parts (such as the joints of the knee, hand, and foot) are foreign tissue and attacks them.
Scleroderma, a chronic autoimmune disease that can lead to inflammation and damage of the skin, joints,
and internal organs.
Ankylosing spondylitis, a disease that involves inflammation of the spine and joints, causing stiffness
and pain.
Juvenile dermatomyositis, a disorder marked by inflammation and damage of the skin and muscles.
Allergic Disorders
Allergic disorders occur when the immune system overreacts to exposure to antigens in the environment. The substances that provoke such attacks are called allergens. The immune response can cause symptoms such as swelling, watery eyes, and sneezing, and even a life-threatening reaction called anaphylaxis. Medications called antihistamines can relieve most symptoms.
Allergic disorders include:
Asthma, a respiratory disorder that can cause breathing problems, frequently involves an allergic response by the
lungs. If the lungs are oversensitive to certain allergens (like pollen, molds, animal dander, or dust mites), it can trigger
breathing tubes in the lungs to become narrowed, leading to reduced airflow and making it hard for a person to breathe.
Eczema is an itchy rash also known as atopic dermatitis. Although atopic dermatitis is not necessarily caused by an
allergic reaction, it more often occurs in kids and teens who have allergies, hay fever, or asthma or who have a family history
of these conditions.
Allergies of several types can occur in kids and teens. Environmental allergies (to dust mites,
for example), seasonal allergies (such as hay fever), drug allergies (reactions to specific medications or drugs), food allergies
(such as to nuts), and allergies to toxins (bee stings, for example) are the common conditions people usually refer to as
allergies.
Cancers of the Immune System
Cancer occurs when cells grow out of control. This also can happen with the cells of the immune system. Lymphoma involves the lymphoid tissues and is one of the more common childhood cancers. Leukemia, which involves abnormal overgrowth of leukocytes, is the most common childhood cancer. With current medications most cases of both types of cancer in kids and teens are curable.
Although immune system disorders usually can't be prevented, you can help your child's immune system stay stronger and fight illnesses by staying informed about your child's condition and working closely with your health care professionals.
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CELLULAR IMMUNE FUNCTION CHEMISTRY Polysaccharide-K, also known as PSK, is a proteoglycan found in several medicinal mushrooms. The results obtained from a large number of published scientific studies and clinical trials show that PSK is a powerful immunomodulator capable of stimulating diverse immunological functions. For instance, PSK can improve cancer survival by restoring and enhancing cellular immune functions in patients with depressed immunity due to radiation and/or chemotherapy or surgical stress after curative resection of cancer. PSK does not interact with other drugs nor affect hepatic drug-metabolizing enzyme activities indicating that drug efficacy is not affected by PSK when used with other medications. PSK is most effective when combined with a front-line anticancer treatment regimen (chemotherapy, radiation therapy or surgery) for patients with many types of cancer. Randomized controlled clinical trials and meta-analysisshowed that overall survival and disease-free survival are improved in patients treated with adjuvant immunotherapy plus PSK. PSK is also beneficial for maintaining general immune health with no reported adverse side effects. They include effects like mitogenicity, and activation of immune effector cells, such as lymphocytes, macrophages, and natural killer cells, resulting in the production of cytokines, including interleukins, tumor necrosis factor alpha, and interferon gamma. One particular effect is the ability to selectively modulate the differentiation capacity of CD4 T cells to mature T helper 1 and or T helper 2 subsets. These effects cause profound effects in response to disease states like chronic autoimmune T helper1 mediated or allergic T helper 2 mediated diseases, like HIV, listeriosis, tuberculosis, septic shock and cancer. Also go to the inflammation mechanisms tab for more information about how the immune system reacts to trauma, diseases and wounds. Various metabolites from mushrooms, Beta-glucans, are reported to affect bone marrow cells, and to induce hematopoiesis. Maitake, caused direct enhancement of the colony forming units, granulocytes/macrophages response of bone marrow cell’s progenitors and enhance recovery of the CFU-GM response after clinically induced hematopoietic suppression. Treatment of macrophages with Reshi increased levels of IL-1B, TNF-a, IL-6 by 5.1, 9.8, and 29 fold respectively, than in control samples. The bactericidal activity of maitake on splenetic T cells was also enhanced, with listeria infected cells by 2.6 times. Excitingly, Shitake interacts with macrophages and related cells and results in the activation of the transcription factor nuclear factor kappa B, which sets off a series of reactions producing a variety of proinflammatory and anti-inflammatory cytokines, TNF-a, IL-1B, IL-10, IL-12, GM-CSF, IL-18, in a sequential manner. The methanol extract of Cordyceps inhibited IL-1B, TNF-a, NO and prostaglandins E2 (PGE2) in vitro and in vivo. The extract inhibited these inflammatory mediators in LPS stimulated murine macrophage cell line by suppressing gene expression of IL-1b, TNF-a, iNOS, and COX-2 through the inhibition of NF kappa beta activation. ____________________________________________________________________________________________________________________________
BIBLIOGRAPHY ____________________________________________________________________________________________________________________________
Cristina Lill, Harry Wichers, and Huub Savelkoul, Anti-inflamatory and Immun-nomodulating properties of Fungal metabolites, Mediators Inflamm, 2005; 2005(2); 63-80 Reshetnikov, Wasser, Tan, Higher basidiomycota as a source of antitumor and immuno-stimulating polysaccharides. Int J Med Mush. 2001;3(4);361-394 Borchers, Stern, Hackman, Mushroom, tumors, and immunity. Proc Soc Exp Biol Med. 1999:221(4):281-293 Gao, Chan, Shou, Immunomodulating activities of Ganoderma, a mushroom with medicinal properties. Food Rev Int. 2004:20:123-161 Li, Huang, Shang et al. The Chinese herbal medicine formula MSSM-002 suppresses allergic airway hyperactivity and modulates TH1/TH2 responses in a murine model of allergic asthma. J Allergy Clin. Immunol. 2000;106(4):660-668 Hsieh, Hsu, Lin, Tsai, Oral administration of an edible mushroom derived protein inhibits the development of food allergic reactions in mice. Clin Exp Allergy. 2003:33(11);1595-1602 Li, Zhang, Huang et al, Food allergy herbal FAHF-1 blocks peanut induced anaphylaxis in a murine model. J Allergy Clin Immunol. 2001:108(4):639-646 Nanba, Kodama, Schar, Turner. Effects of Maitake glucan in HIV infected patients. Mycoscience. 2000;41:293-295 Ngai, Ng,, Lentinan, A novel and potent antifungal protein from Shiitake mushrooms with inhibitory effects on activity of human immunoodefieciency virus-1 reverse transcriptase and proliferation of leukemia cells. Life Sci 2003;73(26);3363-3374 Markova,
Drandarska, Nikolaeva Protective activity of lentinan in experimental tuberculosis. Int Immunopharmecol.
2003;3(10-11):1557-1562 Morphological
and genetic characterization of a cultivated Cordyceps sinensis fungus and its polysaccharide component possessing antioxidant
property in H22 tumor-bearing mice. Chen J, Zhang W, Lu T, Li J, Zheng Y, Kong L.Medical School, Nanjing University, Nanjing 210093, People's
Republic of China.Cordyceps
sinensis, one of the most precious traditional Chinese medicines, possesses the antitumor activity, antioxidant activity and
the capability of modulating the immune system. In the present study, a fungus strain G1 isolated from wild C. sinensis was identified
and initially characterized. A phylogenetic tree was generated based on the sequences of the internal transcribed spacer (ITS)
region of related fungi. The analysis of ITS sequence showed that fungus G1 was clustered together with C. sinensis,
Tolypocladium cylindrosporum and Tolypocladium inflatum in the phylogenetic tree. Both the morphological character and
the ITS sequence analysis establish that fungus G1 is one of the anamorph strains of C. sinensis and belongs to Tolypocladium
genus. Furthermore, the polysaccharide (PS) extracted from fungus G1 and its antioxidant activity on H22-bearing mice
was investigated. H22 cells were hypodermically injected into the right oxter of each mouse after the ICR mice were treated
with PS by means of gavage for 7 days. Then the same administration process continued for 9 days. At the end of
the experiments, the tumor weight of each mouse was measured. Superoxide dismutase (SOD) activity and malondialdehyde (MDA)
level in mouse liver, brain and serum, as well as glutathione peroxidase (GSH-Px) activity in mouse liver and brain were assayed.
The results showed that the H22 tumor growth was significantly inhibited by PS. Moreover,
PS significantly enhanced SOD activity of liver, brain and serum as well as GSH-Px activity of liver and brain in tumor-bearing
mice. PS also significantly reduced the level of MDA in liver and brain of tumor-bearing mice.PMID: 16492382 [PubMed - indexed for
MEDLINE] Related Articles·
Effects of the exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis on immunocytes
of H22 tumor bearing mice. [Fitoterapia. 2008] ·
Mycelium cultivation, chemical composition and antitumour activity of a Tolypocladium sp. fungus
isolated from wild Cordyceps sinensis. [J Appl Microbiol. 2006]
· Effects of exopolysaccharide fraction (EPSF) from a cultivated Cordyceps sinensis fungus on c-Myc,
c-Fos, and VEGF expression in B16 melanoma-bearing mice. [Pathol Res Pract. 2005]
· ReviewCordyceps: a traditional Chinese medicine and another fungal therapeutic biofactory? [Phytochemistry. 2008]
· ReviewThe scientific rediscovery of a precious ancient Chinese herbal regimen: Cordyceps sinensis:
part II. [J Altern Complement Med.
1998] » See Reviews... | » See All... Relation
between Irofulven (MGI-114) systemic exposure and tumor response in human solid tumor xenografts. Leggas M, Stewart CF, Woo MH, Fouladi M, Cheshire PJ, Peterson JK, Friedman HS, Billups C, Houghton PJ.Department of Pharmaceutical Sciences, St. Jude Children's
Research Hospital, Memphis, Tennessee 38105, USA.Irofulven is a novel, small molecular weight semisynthetic compound, derived from a family of
mushroom toxins known as illudins. This DNA alkylating agent has a chemical structure unlike any other chemotherapeutic agent
in clinical use. The molecule is currently being studied in several Phase I, II, and III trials. The objectives of this study
were to evaluate the antitumor activity of Irofulven in a panel of 20 pediatric solid tumor xenografts and to relate the Irofulven
systemic exposure, defined as area under the concentration time curve, to the antitumor dose associated with tumor regression
in the tumor models. Irofulven was administered i.v. daily for 5 days with courses repeated every 21 days for a total of three
cycles. The minimum effective dose of Irofulven causing objective regression (> or =50% volume regression) of advanced
tumors was determined for each of 19 of 20 independently derived tumor models (12 brain tumors, 4 neuroblastomas, and 4 rhabdomyosarcomas).
At the maximum tolerated dose for three cycles of treatment (4.6 mg/kg/day) objective regressions were determined in 14 of
18 tumor lines (78%). However, the dose-response relationship was acute. At 2 mg/kg only 3 of 15 tumors tested demonstrated
objective regressions, and in 3 additional tumors volume regressions were not achieved at a higher dose level (3 mg/kg), hence
were not additionally tested. After administering the maximum tolerated dose (tolerated for one or two cycles of treatment)
of Irofulven, 7 mg/kg, to mice bearing sensitive and resistant human tumors plasma concentration-time profiles were determined.
Tumors were highly sensitive to Irofulven, but the systemic exposure required for a significant rate of objective response
in this panel of tumors is in excess of that achievable in patients at tolerable doses, using this schedule of drug administration.PMID: 12231547 [PubMed - indexed for
MEDLINE] Related Articles·
Enhanced antitumor activity of irofulven in combination with irinotecan in pediatric solid tumor
xenograft models. [Cancer Chemother Pharmacol.
2005] · Synergy of topotecan in combination with vincristine for treatment of pediatric solid tumor xenografts. [Clin Cancer Res. 1999]
· In vivo evaluation of ixabepilone (BMS247550), a novel epothilone B derivative, against pediatric
cancer models. [Clin Cancer Res. 2005]
· ReviewThe role of xenografting in pediatric brain tumor research with specific emphasis on medulloblastoma/primitive
neuroectodermal tumors of childhood. [In Vivo. 2003] ·
ReviewVolumetric considerations in radiotherapy for pediatric parameningeal rhabdomyosarcomas. [Int J Radiat Oncol Biol
Phys. 2003] » See Reviews... | » See All... Patient Drug Information·
Cyclophosphamide (Cytoxan®, Neosar®) Your doctor has ordered the drug cyclophosphamide to help treat your illness. The drug can be taken by mouth in tablet
form or be given by injection into a vein. » read more ... · Daunorubicin (Cerubidine®, DaunoXome®) Your doctor has ordered the drug daunorubicin to help treat your illness. The drug is given by injection into a vein. » read more ... · Doxorubicin (Adriamycin PFS®, Adriamycin RDF®, Adriamycin®, ...) Your doctor has ordered the drug doxorubicin to help treat your illness. The drug is given by injection into a vein. » read more ... » See all 6 Drug Reports ... Nerve growth factor-inducing activity
of Hericium erinaceus in 1321N1 human astrocytoma cells. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N.Department of Cellular Signaling, Graduate School of Pharmaceutical
Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, Japan.Neurotrophic factors are essential to maintain and organize neurons functionally; thereby
neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases
such as Alzheimer's disease. In the present study, we firstly examined the effects of ethanol
extracts of four edible mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake),
and Agaricus blazei (Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among
the four mushroom extracts, only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner.In addition, secretion of NGF protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned
medium of 1321N1 cells incubated with H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones
C, D and E, constituents of H. erinaceus, failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene
expression by H. erinaceus extracts was inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H.
erinaceus extracts induced phosphorylation of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting
that H. erinaceus promotes NGF gene expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in
vivo. ddY mice given feed containing 5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression
in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the
JNK pathway; these compounds are not hericenones.PMID: 18758067 [PubMed - indexed for MEDLINE] Related Articles·
5,19-cyclo-9beta,10xi-androstane-3,17-dione promotes neurotrophic factor biosynthesis in 1321N1
human astrocytoma cells and improves passive avoidance learning impairment. [Brain Res. 2007] ·
Multiple signaling conduits regulate global differentiation-specific gene expression in PC12
cells.[J Cell Physiol. 2004]
· Nerve growth factor-induced up-regulation of cytosolic phospholipase A2alpha level in rat PC12
cells. [Neurosci Lett. 2004]
· ReviewNeuroprotection by NGF in the PC12 in vitro OGD model: involvement of mitogen-activated
protein kinases and gene expression. [Ann N Y Acad Sci. 2005]
· Review[Biochemical studies on functional proteins in the brain nervous system. Neurobiochemical
studies on nerve growth factor] [Yakugaku Zasshi. 1996]
» See Reviews... | » See All... Nerve growth factor-inducing activity of Hericium erinaceus
in 1321N1 human astrocytoma cells. Mori K, Obara Y, Hirota M, Azumi Y, Kinugasa S, Inatomi S, Nakahata N.Department of Cellular Signaling, Graduate School of Pharmaceutical
Sciences, Tohoku University, Aramaki, Aoba-ku, Sendai, Japan. Neurotrophic factors are essential to maintain and organize neurons functionally; thereby
neurotrophic factor-like substances or their inducers are expected to be applied to the treatment of neurodegenerative diseases
such as Alzheimer's disease. In the present study, we first examined the effects of ethanol extracts of four edible
mushrooms, Hericium erinaceus (Yamabushitake), Pleurotus eryngii (Eringi), Grifola frondosa (Maitake), and Agaricus blazei
(Himematsutake), on nerve growth factor (NGF) gene expression in 1321N1 human astrocytoma cells. Among the four mushroom extracts,
only H. erinaceus extract promoted NGF mRNA expression in a concentration-dependent manner. In addition, secretion of NGF
protein from 1321N1 cells was enhanced by H. erinaceus extracts, and the conditioned medium of 1321N1 cells incubated with
H. erinaceus extract enhanced the neurite outgrowth of PC12 cells. However, hericenones C, D and E, constituents of H. erinaceus,
failed to promote NGF gene expression in 1321N1 cells. The enhancement of NGF gene expression by H. erinaceus extracts was
inhibited by the c-jun N-terminal kinase (JNK) inhibitor SP600125. In addition, H. erinaceus extracts induced phosphorylation
of JNK and its downstream substrate c-Jun, and increased c-fos expression, suggesting that H. erinaceus promotes NGF gene
expression via JNK signaling. Furthermore we examined the efficacy of H. erinaceus in vivo. ddY mice given feed containing
5% H. erinaceus dry powder for 7 d showed an increase in the level of NGF mRNA expression in the hippocampus. In conclusion, H. erinaceus contains active compounds that stimulate NGF synthesis via activation of the
JNK pathway; these compounds are not hericenones. PMID: 18758067 [PubMed - indexed for MEDLINE] Related Articles·
5,19-cyclo-9beta,10xi-androstane-3,17-dione promotes neurotrophic factor biosynthesis in 1321N1
human astrocytoma cells and improves passive avoidance learning impairment. [Brain Res. 2007] ·
Multiple signaling conduits regulate global differentiation-specific gene expression in PC12
cells.[J Cell Physiol. 2004]
· Nerve growth factor-induced up-regulation of cytosolic phospholipase A2alpha level in rat PC12
cells. [Neurosci Lett. 2004]
· Review Neuroprotection by NGF in the PC12 in vitro OGD model: involvement of mitogen-activated
protein kinases and gene expression. [Ann N Y Acad Sci. 2005]
Review[Biochemical studies on functional proteins in the brain nervous system. Neurobiochemical
studies on nerve growth factor] [Yakugaku
Zasshi. 1996]
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