Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The tumor suppressor gene p16/MTS1, located on chromosome 9p21, is a cell cycle regulatory gene which is frequently altered in human cancers. The role of this gene in prostate cancer is unknown. To determine the frequency of deletions and point mutations of p16/MTS1 in human prostate cancer, we examined 18 cancer and matched benign and hyperplastic tissue specimens. Deletions of p16/MTS1 were detected by semi-quantitative multiplex polymerase chain reaction in which a portion of exon 2 of the p16/MTS1 gene and a control marker, the glyceraldehyde 3-phosphate dehydrogenase gene, were amplified simultaneously. 'Cold' single-stranded conformational polymorphism (SSCP) analysis was performed to examine exons 1 and 2 of the p16/MTS1 gene for point mutations. Our data indicate no evidence for intragenic homozygous deletion in the prostate tumors. One prostate tumor and matched benign tissue showed mobility shifts. Direct DNA sequencing of the SSCP positive samples showed a G --> A transition in codon 140 which would result in an amino acid change from alanine to threonine. Our results indicate that deletions and point mutations in the p16/MTS1 gene are rare and do not play a major role in human prostate carcinogenesis.
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PMID:Absence of p16/MTS1 gene mutations in human prostate cancer. 900 95

To investigate molecular mechanisms controlling plant morphogenesis, we examined the morphology of primary roots of Arabidopsis thaliana and the organization of cortical microtubules in response to inhibitors of serine/threonine protein phosphatases and kinases. We found that cantharidin, an inhibitor of types 1 and 2A protein phosphatases, as previously reported for okadaic acid and calyculin A (R.D. Smith, J.E. Wilson, J.C. Walker, T.I. Baskin [1994] Planta 194: 516-524), inhibited elongation and stimulated radial expansion. Of the protein kinase inhibitors tested, chelerythrine, 6-dimethylaminopurine, H-89, K252a, ML-9, and staurosporine all inhibited elongation, but only staurosporine appreciably stimulated radial expansion. To determine the basis for the root swelling, we examined cortical microtubules in semithin sections of material embedded in butyl-methyl-methacrylate. Chelerythrine and 100 nM okadaic acid, which inhibited elongation without causing swelling, did not change the appearance of cortical arrays, but calyculin A, cantharidin, and staurosporine, which caused swelling, disorganized cortical microtubules. The stability of the microtubules in the aberrant arrays was not detectably different from those in control arrays, as judged by similar sensitivity to depolymerization by cold or oryzalin. These results identify protein phosphorylation and dephosphorylation as requirements in one or more steps that organize the cortical array of microtubules.
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PMID:Inhibitors of protein kinases and phosphatases alter root morphology and disorganize cortical microtubules. 904 96

Protein phosphatase 2A (PP2A) is a major cellular serine/threonine protein phosphatase, present in the cell in a variety of heterotrimeric forms that differ in their associated regulatory B-subunit. Cloning of the mammalian B' subunit has allowed the identification of a highly homologous Saccharomyces cerevisiae gene, RTS1. Disruption of the gene results in a temperature-sensitive growth defect that can be suppressed by expression of rabbit B'alpha or B'gamma isoforms. The B'alpha subunit is much more effective in restoring normal growth at 37 degrees C than B'gamma. Immunoprecipitated Rts1p was found associated with type 2A-specific protein phosphatase activity that is sensitive to 2 nM okadaic acid, but not to 100 nM phosphatase inhibitor-2, and to be phosphorylated in vivo. However, overexpression of RTS1 was unable to suppress the cold sensitivity, defective cytokinesis, and abnormal cell morphology resulting from defects in the CDC55 gene, which encodes the yeast homolog of a different B subunit of another form of 2A phosphatase, PP2A1. These results indicate that Rts1p is a yeast homolog of the mammalian B' subunit and that the various regulatory B-subunits of PP2A are not functionally redundant but direct the enzyme to distinct cellular functions.
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PMID:Saccharomyces cerevisiae homologs of mammalian B and B' subunits of protein phosphatase 2A direct the enzyme to distinct cellular functions. 907 45

Three cold-sensitive mutants in phage P22 coat protein have been characterized to determine the effects of the amino acid substitutions that cause cold sensitivity on the folding pathway and the conformation of refolded coat protein. Here we find that the three cold-sensitive mutants which have the threonine residue at position 10 changed to isoleucine (T10I), the arginine residue at position 101 changed to cysteine (R101C), or the asparagine residue at position 414 changed to serine (N414S) were capable of folding from a denatured state into a soluble monomeric species, but in each case, the folded conformation was altered. Changes in the kinetics of folding were observed by both tryptophan and bisANS fluorescence. In contrast to the temperature-sensitive for folding coat protein mutants which can be rescued at nonpermissive temperatures in vivo by the overproduction of molecular chaperones GroEL and GroES [Gordon, C. L., Sather, S. K., Casjens, S., & King, J. (1994) J. Biol. Chem. 269, 27941-27951], the folding defects associated with the cold-sensitive amino acid substitutions were not recognized by GroEL and GroES.
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PMID:The folded conformation of phage P22 coat protein is affected by amino acid substitutions that lead to a cold-sensitive phenotype. 909 27

Freezing avoidance conferred by different types of antifreeze proteins in various polar and subpolar fishes represents a remarkable example of cold adaptation, but how these unique proteins arose is unknown. We have found that the antifreeze glycoproteins (AFGPs) of the predominant Antarctic fish taxon, the notothenioids, evolved from a pancreatic trypsinogen. We have determined the likely evolutionary process by which this occurred through characterization and analyses of notothenioid AFGP and trypsinogen genes. The primordial AFGP gene apparently arose through recruitment of the 5' and 3' ends of an ancestral trypsinogen gene, which provided the secretory signal and the 3' untranslated region, respectively, plus de novo amplification of a 9-nt Thr-Ala-Ala coding element from the trypsinogen progenitor to create a new protein coding region for the repetitive tripeptide backbone of the antifreeze protein. The small sequence divergence (4-7%) between notothenioid AFGP and trypsinogen genes indicates that the transformation of the proteinase gene into the novel ice-binding protein gene occurred quite recently, about 5-14 million years ago (mya), which is highly consistent with the estimated times of the freezing of the Antarctic Ocean at 10-14 mya, and of the main phyletic divergence of the AFGP-bearing notothenioid families at 7-15 mya. The notothenioid trypsinogen to AFGP conversion is the first clear example of how an old protein gene spawned a new gene for an entirely new protein with a new function. It also represents a rare instance in which protein evolution, organismal adaptation, and environmental conditions can be linked directly.
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PMID:Evolution of antifreeze glycoprotein gene from a trypsinogen gene in Antarctic notothenioid fish. 910 60

Mice made cold water swimming (CWS: 4 degrees C, 3 min) produced an opioid-mediated antinociception. Experiments were designed to determine what types of opioid receptors and endogenous opioid peptides in the spinal cord are involved in the CWS-induced antinociception in male ICR mice. Antinociception was measured by the tail-flick test. CWS-induced antinociception was blocked by intrathecal (i.t.) pretreatment with antiserum to [Met5]enkephalin (100 microg, 1 hr), but not by antiserum (100 microg, 1 hr) to [Leu5]enkephalin, beta-endorphin or dynorphin A (1-17). Moreover, i.t. pretreatment with delta2-opioid receptor antagonist naltriben (NTB: 10 microg, 10 min) blocked the antinociception induced by CWS or i.t.-administered [Met5]enkephalin (10 microg). However, the antinociception induced by CWS or i.t.-administered [Met5]enkephalin was not blocked by i.t. pretreatment with delta1-opioid receptor antagonist 7-benzylidene naltrexone (BNTX: 1 microg, 10 min), mu-opioid receptor antagonist D-Phe-Cys-Try-D-Try-Om-Thr-Phe-Thr-NH2 (CTOP: 50 ng, 10 min), or kappa-opioid receptor antagonist norbinaltorphimine (norBNI: 5 microg, 24 hr). These data indicate that [Met5]enkephalin and delta2-opioid receptor in the spinal cord are involved in antinociception induced by CWS.
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PMID:[Met5]enkephalin and delta2-opioid receptors in the spinal cord are involved in the cold water swimming-induced antinociception in the mouse. 925 52

A cold-adapted protease subtilisin was successfully isolated by evolutionary engineering based on sequential in vitro random mutagenesis and an improved method of screening (H. Kano, S. Taguchi, and H. Momose, Appl. Microbiol. Biotechnol. 47:46-51, 1997). The mutant subtilisin, termed m-63, exhibited a catalytic efficiency (expressed as the kcat/Km value) 100% higher than that of the wild type at 10 degrees C when N-succinyl-L-Ala-L-Ala-L-Pro-L-Phe-p-nitroanilide was used as a synthetic substrate. This cold adaptation was achieved with three mutations, Val to Ile at position 72 (V72I), Ala to Thr at position 92 (A92T), and Gly to Asp at position 131 (G131D), and it was found that an increase in substrate affinity (i.e., a decreased Km value) was mostly responsible for the increased activity. Analysis of kinetic parameters revealed that the V72I mutation contributed negatively to the activity but that the other two mutations, A92T and G131D, overcame the negative contribution to confer the 100% increase in activity. Besides suppression of the activity-negative mutation (V72I) by A92T and G131D, suppression of structural stability was observed in measurements of activity retention at 60 degrees C and circular dichroism spectra at 10 degrees C.
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PMID:Engineering of a cold-adapted protease by sequential random mutagenesis and a screening system. 946 83

The minor chlorophyll a/b-binding (CAB) proteins of the liverwort Marchantia polymorpha L. were investigated in order to compare the antenna organization and the light-acclimation potential in lower and higher plants. Homologues to the minor CAB proteins CP24, CP26 and CP29 were identified by the following criteria: enrichment in photosystem II preparations, immunological cross-reactivities, spectroscopic properties and protein-fragment amino acid sequences. The high violaxanthin content of the minor CAB proteins in M. polymorpha indicates that their role in protection from high light is comparable in lower and higher plants. Considerably more-alkaline isoelectric points are found for the minor CAB proteins of M. polymorpha than for their higher-plant counterparts. This might be due to a higher content of basic amino acids. While the N-terminal sequence of angiosperm CP29 contains a threonine that becomes phosphorylated during cold stress, this amino acid is substituted by valine in M. polymorpha. Therefore, the regulatory properties of this protein could differ in lower and higher plants.
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PMID:Identification and characterization of photosystem II chlorophyll a/b binding proteins in Marchantia polymorpha L. 948 29

We have previously reported that ischemic spinal cord injury in rats leads to chronic pain-related behaviors. Thus, rats exhibited aversive reactions to innocuous mechanical stimuli (mechanical allodynia) applied to a body area at or rostral to the dermatomes innervated by the injured spinal segments. The responses of the rats to cold are also markedly enhanced (cold allodynia). Interestingly, more than 50% of spinally injured rats did not develop these abnormal pain-related behaviors after spinal cord injury. In the present study, we showed that the extent of injury is similar between allodynic and non-allodynic rats. Furthermore, intrathecal (i.t.) naloxone, a broad-spectrum opioid receptor antagonist, reversibly provoked mechanical and cold allodynia-like responses in spinally injured rats that did not develop such behaviors spontaneously. However, naloxone did not elicit such reactions in normal rats and did not alter the tail-flick latency in normal or spinally injured rats. Furthermore, i.t. D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) or naltridole, selective antagonists of mu and delta opioid receptors, respectively, also triggered pain-related behaviors similarly to naloxone. Although norbinaltorphimine (nor-BIN), a selective kappa-receptor antagonist, also elicited such responses, the time course of the effect makes it unlikely that spinal kappa-receptors were involved. These results suggested that the expression of abnormal pain-related behaviors in some spinally injured rats is tonically suppressed by the spinal opioidergic system. Interindividual differences that lead to lack or dysfunction of such inhibition may underly the appearence of pain-related behavior in some, but not all, spinally injured rats. It is suggested that such inhibition is exerted through spinal mu and delta, but not kappa, opioid receptors. The endogenous opioidergic control appears to be only active against abnormal painrelated behaviors in spinally injured rats. Our results are relevant for the clinical observation that only a subgroup of patients with nerve injury suffers from neuropathic pain.
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PMID:Evidence that spinal endogenous opioidergic systems control the expression of chronic pain-related behaviors in spinally injured rats. 954 96

We examined the effects of intrathecal (i.t.) selective opioid receptor agonists in alleviating mechanical and cold allodynia in spinally injured rats. Both DAMGO ([D-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin, a mu-opioid receptor agonist) and DPDPE ([D-Phe2,D-Phe5]-enkephalin, a delta-opioid receptor agonist) dose-dependently relieved the chronic allodynia-like behavior at doses selective for their respective receptors. The anti-allodynic effect of DAMGO and DPDPE was reversed by the selective mu- and delta-opioid receptor antagonists CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2) and naltrindole, respectively. In contrast, the selective kappa-opioid receptor agonist U50488H did not alleviate the allodynia-like behavior, but rather enhanced it. The anti-nociceptive and anti-allodynic effect of i.t. DAMGO was blocked by U50488H. Thus, activation of spinal mu- and delta-, but not kappa-opioid receptors produced anti-allodynic effect in this model of central pain. Drugs which act selectively on opioid receptor subtypes may be useful in managing chronic central pain of spinal cord origin.
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PMID:Treatment of chronic allodynia in spinally injured rats: effects of intrathecal selective opioid receptor agonists. 958 56


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