Interleukin-1 beta induces posttranslational carboxymethylation and alterations in subnuclear distribution of lamin B in insulin-secreting RINm5F cells.

We examined the effects of interleukin-1beta (IL-1beta) treatment on the distribution and degradation of lamin B in the nuclear fraction from insulin-secreting RINm5F cells. Western blot analysis indicated that IL-1beta treatment caused significant alterations in the redistribution of lamin B, specifically between the Triton X-100-soluble (membrane) and -insoluble (matrix) fractions of the nucleus. IL-1beta treatment also increased the lamin carboxymethyltransferase activity and the relative abundance of the carboxymethylated lamin in the nuclear fraction. A significant increase in the relative abundance of lamin B degradation products was also observed in the nuclear fraction from the IL-1beta-treated cells. These findings are compatible with a measurable increase in the lamin-degrading caspase-6 activity in IL-1beta-treated cells. Confocal microscopic observation of IL-1beta-treated cells suggested a significant dissociation of lamin B from the nuclear lamina and its subsequent association with the DNA-rich elements within the nucleus. N(G)-monomethyl-l-arginine, a known inhibitor of inducible nitric oxide synthetase (iNOS), markedly inhibited IL-1beta-induced iNOS gene expression, NO release, caspase-3 and caspase-6 activation, lamin B degradation, and loss of metabolic cell viability, indicating that the observed IL-1beta-induced effects on nuclear lamin B involve the intermediacy of NO. Together, our data support the hypothesis that IL-1beta treatment results in significant increase in the carboxymethylation of lamin B, which would place lamin B in a strategic location for its degradation mediated by caspases. This could possibly lead to dissolution of the nuclear envelope, culminating in the demise of the effete beta-cell.

[1]  M. Mcdaniel,et al.  cAMP Dose-dependently Prevents Palmitate-induced Apoptosis by Both Protein Kinase A- and cAMP-Guanine Nucleotide Exchange Factor-dependent Pathways in β-Cells* , 2004, Journal of Biological Chemistry.

[2]  A. Kowluru,et al.  Regulation by glucose and calcium of the carboxylmethylation of the catalytic subunit of protein phosphatase 2A in insulin-secreting INS-1 cells. , 2004, American journal of physiology. Endocrinology and metabolism.

[3]  A. Kowluru,et al.  Novel roles for palmitoylation of Ras in IL-1β-induced nitric oxide release and caspase 3 activation in insulin-secreting β cells , 2003 .

[4]  H. Mischak,et al.  Protein Kinase C δ Activation and Translocation to the Nucleus Are Required for Fatty Acid-Induced Apoptosis of Insulin-Secreting Cells , 2003 .

[5]  A. Kowluru,et al.  IL-1beta-induced nitric oxide release from insulin-secreting beta-cells: further evidence for the involvement of GTP-binding proteins. , 2002, Diabetes & metabolism.

[6]  K. Mani,et al.  Copper-dependent Autocleavage of Glypican-1 Heparan Sulfate by Nitric Oxide Derived from Intrinsic Nitrosothiols* , 2002, The Journal of Biological Chemistry.

[7]  M. Bergo,et al.  Membrane trafficking of heterotrimeric G proteins via the endoplasmic reticulum and Golgi. , 2002, Molecular biology of the cell.

[8]  M. Kitazawa,et al.  Caspase-3-dependent Proteolytic Cleavage of Protein Kinase C␦ Is Essential for Oxidative Stress-mediated Dopaminergic Cell Death after Exposure to Methylcyclopentadienyl Manganese Tricarbonyl , 2022 .

[9]  T. Mandrup-Poulsen,et al.  A choice of death – the signal-transduction of immune-mediated beta-cell apoptosis , 2001, Diabetologia.

[10]  C. Fiorentini,et al.  Positive modulation by Ras of interleukin-1β-mediated nitric oxide generation in insulin-secreting clonal β (HIT-T15) cells , 2001 .

[11]  R. Moir,et al.  The structure and function of nuclear lamins: implications for disease , 2001, Cellular and Molecular Life Sciences CMLS.

[12]  F. Sobrino,et al.  Sodium nitroprusside-induced mitochondrial apoptotic events in insulin-secreting RINm5F cells are associated with MAP kinases activation. , 2001, Experimental cell research.

[13]  J. Contreras,et al.  A tripartite anoikis-like mechanism causes early isolated islet apoptosis. , 2001, Surgery.

[14]  Yigong Shi,et al.  A structural view of mitochondria-mediated apoptosis , 2001, Nature Structural Biology.

[15]  R. Goldman,et al.  Disruption of Nuclear Lamin Organization Blocks the Elongation Phase of DNA Replication , 2000, The Journal of cell biology.

[16]  J. Lord,et al.  PKC-δ is an apoptotic lamin kinase , 2000, Oncogene.

[17]  M. Cohen,et al.  Review: nuclear lamins--structural proteins with fundamental functions. , 2000, Journal of structural biology.

[18]  A. Kowluru.  Evidence for the carboxyl methylation of nuclear lamin-B in the pancreatic beta cell. , 2000, Biochemical and biophysical research communications.

[19]  K. Utsumi,et al.  Caspase activation and cytochrome c release during HL-60 cell apoptosis induced by a nitric oxide donor , 2000, Free radical research.

[20]  F. Sobrino,et al.  Methylation-Dependent Gene Silencing Induced by Interleukin 1β via Nitric Oxide Production , 1999, The Journal of experimental medicine.

[21]  C. Richter,et al.  Mitochondrial nitric-oxide synthase stimulation causes cytochrome c release from isolated mitochondria. Evidence for intramitochondrial peroxynitrite formation. , 1999, The Journal of biological chemistry.

[22]  F. Sobrino,et al.  NO induces a cGMP‐independent release of cytochrome c from mitochondria which precedes caspase 3 activation in insulin producing RINm5F cells , 1999, FEBS letters.

[23]  B. Buendia,et al.  Caspase-dependent proteolysis of integral and peripheral proteins of nuclear membranes and nuclear pore complex proteins during apoptosis. , 1999, Journal of cell science.

[24]  B. Brüne,et al.  Nitric Oxide-induced S-Glutathionylation and Inactivation of Glyceraldehyde-3-phosphate Dehydrogenase* , 1999, The Journal of Biological Chemistry.

[25]  A. Krystosek.  Preferential sites of early DNA cleavage in apoptosis and the pathway of nuclear damage , 1999, Histochemistry and Cell Biology.

[26]  M. Green,et al.  Insulin secretion, DNA damage, and apoptosis in human and rat islets of Langerhans following exposure to nitric oxide, peroxynitrite, and cytokines. , 1998, Nitric oxide : biology and chemistry.

[27]  J C Reed,et al.  Mitochondria and apoptosis. , 1998, Science.

[28]  W. Suarez-Pinzon,et al.  Cytokines and their roles in pancreatic islet beta-cell destruction and insulin-dependent diabetes mellitus. , 1998, Biochemical pharmacology.

[29]  M. Rabaglia,et al.  Evidence for differential roles of the Rho subfamily of GTP-binding proteins in glucose- and calcium-induced insulin secretion from pancreatic beta cells. , 1997, Biochemical pharmacology.

[30]  M. Hoenig,et al.  Subnuclear Localization of Protein Kinase C δ in Beta Cells , 1997 .

[31]  A. Kowluru,et al.  Glucose activates the carboxyl methylation of gamma subunits of trimeric GTP-binding proteins in pancreatic beta cells. Modulation in vivo by calcium, GTP, and pertussis toxin. , 1997, The Journal of clinical investigation.

[32]  P. Collas,et al.  Protein Kinase C-mediated Interphase Lamin B Phosphorylation and Solubilization* , 1997, The Journal of Biological Chemistry.

[33]  M. Nehls,et al.  Suppression of Apoptosis by Nitric Oxide via Inhibition of Interleukin-1β–converting Enzyme (ICE)-like and Cysteine Protease Protein (CPP)-32–like Proteases , 1997, The Journal of experimental medicine.

[34]  E. White,et al.  Lamin proteolysis facilitates nuclear events during apoptosis , 1996, The Journal of cell biology.

[35]  T. Mandrup-Poulsen,et al.  The role of interleukin-1 in the pathogenesis of IDDM , 1996, Diabetologia.

[36]  M. Shimaoka,et al.  Nitric oxide induces apoptosis in mouse splenic T lymphocytes. , 1996, Immunology letters.

[37]  A. Chinnaiyan,et al.  The CED-3/ICE-like Protease Mch2 Is Activated during Apoptosis and Cleaves the Death Substrate Lamin A* , 1996, The Journal of Biological Chemistry.

[38]  A. Kowluru,et al.  Characterization of prenylcysteine methyltransferase in insulin-secreting cells. , 1996, The Biochemical journal.

[39]  N. Neamati,et al.  Degradation of lamin B1 precedes oligonucleosomal DNA fragmentation in apoptotic thymocytes and isolated thymocyte nuclei. , 1995, Journal of immunology.

[40]  C. Martínez-A,et al.  Splenic B lymphocyte programmed cell death is prevented by nitric oxide release through mechanisms involving sustained Bcl-2 levels. , 1995, The Journal of clinical investigation.

[41]  G. Fröschl,et al.  Chromatin condensation during apoptosis is accompanied by degradation of lamin A+B, without enhanced activation of cdc2 kinase , 1994, The Journal of cell biology.

[42]  J. Bach,et al.  Insulin-dependent diabetes mellitus as an autoimmune disease. , 1994, Endocrine reviews.

[43]  E. Nigg,et al.  The role of isoprenylation in membrane attachment of nuclear lamins. A single point mutation prevents proteolytic cleavage of the lamin A precursor and confers membrane binding properties. , 1994, Journal of cell science.

[44]  E. Cagliero,et al.  Interleukin‐1β induces the expression of an isoform of nitric oxide synthase in insulin‐producing cells, which is similar to that observed in activated macrophages , 1992 .

[45]  D. Chelsky,et al.  COOH-terminal methylation of lamin B and inhibition of methylation by farnesylated peptides corresponding to lamin B and other CAAX motif proteins. , 1992, The Journal of biological chemistry.

[46]  E. Nigg,et al.  The CaaX motif is required for isoprenylation, carboxyl methylation, and nuclear membrane association of lamin B2 , 1991, The Journal of cell biology.

[47]  L. Beck,et al.  Isoprenylation is required for the processing of the lamin A precursor , 1990, The Journal of cell biology.

[48]  M. Gelb,et al.  Human lamin B contains a farnesylated cysteine residue. , 1989, The Journal of biological chemistry.

[49]  E. Nigg,et al.  Modification of nuclear lamin proteins by a mevalonic acid derivative occurs in reticulocyte lysates and requires the cysteine residue of the C‐terminal CXXM motif. , 1989, The EMBO journal.

[50]  S. Kaufmann.  Induction of endonucleolytic DNA cleavage in human acute myelogenous leukemia cells by etoposide, camptothecin, and other cytotoxic anticancer drugs: a cautionary note. , 1989, Cancer research.

[51]  C. O'Neill,et al.  Lamin B methylation and assembly into the nuclear envelope. , 1989, The Journal of biological chemistry.

[52]  J. Glomset,et al.  Evidence for modification of lamin B by a product of mevalonic acid. , 1988, The Journal of biological chemistry.

[53]  D. Koshland,et al.  Cell cycle-dependent methyl esterification of lamin B. , 1987, The Journal of biological chemistry.

[54]  M. M. Bradford.  A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. , 1976, Analytical biochemistry.

[55]  P. Walker,et al.  Degradation of nuclear matrix and DNA cleavage in apoptotic thymocytes. , 1996, Journal of cell science.

[56]  R. Goldman,et al.  The dynamic properties and possible functions of nuclear lamins. , 1995, International review of cytology.