Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0751781 (NOD)
 6,696 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

17 members of MIP family from bacteria, yeast, plants and animals are compared in this review. These proteins appear to function in (1) water channels (CHIP, WCH-CD, MIWC, AQP3, gTIP, RD28, TobRB7), (2) neurogenesis (Bib), (3) small-molecule-permeating channels (MIP, AQP3, NOD, Glpf), (4) unknown function (WCH-3, AtRB7, Pea R7A, FPS1). However, the biological functions are not well established. The most conserved residues in the first and the second halves of all MIP family proteins are asparagine-proline-alanine (NPA) sequences in the loops (NPA boxes). This structural similarity may lead to functional similarity (water and/or small molecule permeation). This signature sequence for the MIP family will facilitate the identification of new protein members of this family.
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PMID:[Water channel family proteins]. 753 36

The major intrinsic protein (MIP) of the bovine lens fiber cell membrane was the first member of the MIP family of proteins to be sequenced and characterized. It is probably a homotetramer with transmembrane channel activity that plays a role in lens biogenesis or maintenance. The polypeptide chain of each subunit may span the membrane six times, and both the N- and C-termini face the cell cytoplasm. Eighteen sequenced or partially sequenced proteins from bacteria, yeast, plants, and animals have now been shown to be members of the MIP family. These proteins appear to function in (1) metazoan development and neurogenesis (MIP and BIB), (2) water transport across the human erythrocyte membrane (ChIP), (3) communication between host plant cells and symbiotic nitrogen-fixing bacteria (NOD), (4) transport across the tonoplast membrane during plant seed development (alpha-TIP), (5) water stress-induced resistance to desiccation in plants (Wsi-TIP), (6) suppression of a genetic growth defect on fermentable sugars in yeast (FPS1), and (7) transport of glycerol across bacterial cell membranes (GlpF). One other sequenced member of the MIP family (ORF1 of Lactococcus lactis) has no known physiological function. The biochemical functions of the eukaryotic proteins are not well established. Computer analyses have revealed that the first and second halves of all MIP family proteins probably arose by a tandem, intragenic, duplication event. Thus, the primary structure of putative transmembrane helices 1 to 3 is similar to that of putative transmembrane helices 4 to 6 even though they are of opposite orientation in the membrane. Among the most conserved residues in these two repeated halves are a membrane-embedded glutamate (E) in helices 1 and 4, an asparagine-proline-alanine (NPA) sequence in the loops between helices 2 and 3 (cytoplasmically localized) and helices 5 and 6 (extracellularly localized), and a glycine within helices 3 and 6. Statistical analyses suggest that the two halves of these proteins have evolved to serve distinct functions: the first half is more important for the generalized or common functions of these proteins, while the second half of these proteins is more differentiated to provide specific or dissimilar functions of the proteins. The apparent origin of MIP family proteins by duplication of a three-spanner precursor protein suggests an evolutionary origin distinct from other transport proteins with six transmembrane spanners.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The MIP family of integral membrane channel proteins: sequence comparisons, evolutionary relationships, reconstructed pathway of evolution, and proposed functional differentiation of the two repeated halves of the proteins. 832 40

CVD (cardiovascular disease) represents a leading cause of mortality in chronic SCI (spinal cord injury). Several component risk factors are observed in SCI; however, the underlying mechanisms that contribute to these risks have not been defined. Central and peripheral chronic inflammation is associated with metabolic dysfunction and CVD, including adipokine regulation of neuroendocrine and cardiac function and inflammatory processes initiated by the innate immune response. We use female C57 Bl/6 mice to examine neuroendocrine, cardiac, adipose and pancreatic signaling related to inflammation and metabolic dysfunction in response to experimentally induced chronic SCI. Using immuno-histochemical, -precipitation, and -blotting analysis, we show decreased POMC (proopiomelanocortin) and increased NPY (neuropeptide-Y) expression in the hypothalamic ARC (arcuate nucleus) and PVN (paraventricular nucleus), 1-month post-SCI. Long-form leptin receptor (Ob-Rb), JAK2 (Janus kinase)/STAT3 (signal transducer and activator of transcription 3)/p38 and RhoA/ROCK (Rho-associated kinase) signaling is significantly increased in the heart tissue post-SCI, and we observe the formation and activation of the NLRP3 (NOD-like receptor family, pyrin domain containing 3) inflammasome in VAT (visceral adipose tissue) and pancreas post-SCI. These data demonstrate neuroendocrine signaling peptide alterations, associated with central inflammation and metabolic dysfunction post-SCI, and provide evidence for the peripheral activation of signaling mechanisms involved in cardiac, VAT and pancreatic inflammation and metabolic dysfunction post-SCI. Further understanding of biological mechanisms contributing to SCI-related inflammatory processes and metabolic dysfunction associated with CVD pathology may help to direct therapeutic and rehabilitation countermeasures.
ASN Neuro 2013 Sep 04
PMID:Neuroendocrine and cardiac metabolic dysfunction and NLRP3 inflammasome activation in adipose tissue and pancreas following chronic spinal cord injury in the mouse. 2392 18

We and others have reported that the anticancer activity of L-asparaginase (ASNase) against asparagine synthetase (ASNS)-positive cell types requires ASNase glutaminase activity, whereas anticancer activity against ASNS-negative cell types does not. Here, we attempted to disentangle the relationship between asparagine metabolism, glutamine metabolism, and downstream pathways that modulate cell viability by testing the hypothesis that ASNase anticancer activity is based on asparagine depletion rather than glutamine depletion per se. We tested ASNase wild-type (ASNaseWT) and its glutaminase-deficient Q59L mutant (ASNaseQ59L) and found that ASNase glutaminase activity contributed to durable anticancer activity against xenografts of the ASNS-negative Sup-B15 leukemia cell line in NOD/SCID gamma mice, whereas asparaginase activity alone yielded a mere growth delay. Our findings suggest that ASNase glutaminase activity is necessary for durable, single-agent anticancer activity in vivo, even against ASNS-negative cancer types.
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PMID:Glutaminase Activity of L-Asparaginase Contributes to Durable Preclinical Activity against Acute Lymphoblastic Leukemia. 3120 81