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Biomedical subjects

Peter M Steinert

Publications and source records attributed to Peter M Steinert.

23 records · Page 2Linked to original sources
PubMed2002

Transglutaminases in disease.

Transglutaminases (TGases) are enzymes that are widely used in many biological systems for generic tissue stabilization purposes. Mutations resulting in lost activity underlie several serious disorders. In addition, new evidence documents that they may also be aberrantly activated in tissues and cells and contribute to a variety of diseases, including neurodegenerative diseases such as Alzheimer's and Huntington's diseases. In these cases, the TGases appear to be a factor in the formation of inappropriate proteinaceous aggregates that may be cytotoxic. In other cases such as celiac disease, however, TGases are involved in the generation of autoantibodies. Further, in diseases such as progressive supranuclear palsy, Huntington's, Alzheimer's and Parkinson's diseases, the aberrant activation of TGases may be caused by oxidative stress and inflammation. This review will examine the role and activation of TGases in a variety of diseases.

Arteriosclerosis↗
PubMed2002

Cell-cell adhesion and RhoA-mediated actin polymerization are independent phenomena in microtubule disrupted keratinocytes.

E-cadherin-mediated adherens junction formation and maintenance are thought to involve actin filament rearrangements through the action of small GTPases. Recently, we demonstrated that microtubule disruption in normal human epidermal keratinocytes grown in low calcium media conditions induces cell-cell adhesion by redistribution of endogenous E-cadherin, and it promotes stress fiber formation. This actin rearrangement was apparently mediated by RhoA activation. This model system therefore provides a tool with which to dissect relationships between cell-cell adhesion and Rho-mediated stress fiber formation. In this study, we have demonstrated in normal human epidermal keratinocytes that disruption of actin structures including stress fibers does not interfere with E-cadherin redistribution during microtubule-induced cell-cell adhesion. Moreover, this cell-cell adhesion could not be blocked by RhoA inactivation at the level for inhibition of stress fiber formation. Additionally, in the immortalized HaCaT keratinocyte cell line, which does not undergo cell-cell adhesion after microtubule disruption in low calcium conditions, expression of dominant-active RhoA could induce stress fiber formation without inducing adhesion. On the other hand, a variant of the HaCaT cell line, HC-R1, showed microtubule-disruption-induced cell-cell adhesion without stress fiber formation. Together, our results suggest that, in keratinocytes, the process of cell adhesion can occur independently of RhoA-mediated stress fiber formation.

Actins↗
PubMed2002

IFN-gamma induces transglutaminase 2 expression in rat small intestinal cells.

Transglutaminase 2 (tissue transglutaminase, TGase 2) was recently identified as an endomysial autoantigen in celiac disease (CD). Identification of how TGase 2 expression is increased may allow a better understanding of this autoimmune disease. Certain inflammatory cytokines, tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), and the Th type I cytokine interferon-gamma (INF-gamma) are abundant in CD. We have investigated whether these play a role in the regulation of TGase 2 expression in a model rat small intestinal epithelial cell line (IEC-6). After treatment for 24 h, TNF-alpha did not significantly alter TGase 2 mRNA or activity, but TGF-beta decreased mRNA and activity by 4-5-fold. IFN-gamma increased mRNA and TGase 2 activity by about 2-fold in 24 h and 5-fold by 5 days. Our new data suggest that increased TGase 2 expression in the upper small intestine of CD patients may be due to increased IFN-gamma expression, loss of TGF-beta signaling, or both.

Animals↗
PubMedDate not supplied

A role for the 1A and L1 rod domain segments in head domain organization and function of intermediate filaments: structural analysis of trichocyte keratin.

A dynamic model is proposed to explain how the 1A and linker L1 segments of the rod domain in intermediate filament (IF) proteins affect the head domain organization and vice versa. We have shown in oxidized trichocyte IF that the head domain sequences fold back over and interact with the rod domain. This phenomenon may occur widely in reduced IF as well. Its function may be to stabilize the 1A segments into a parallel two-stranded coiled coil or something closely similar. Under differing reversible conditions, such as altered states of IF assembly, or posttranslational modifications, such as phosphorylation etc., the head domains may no longer associate with the 1A segment. This could destabilize segment 1A and cause the two alpha-helical strands to separate. Linker L1 would thus act as a hinge and allow the heads to function over a wide lateral range. This model has been explored using the amino acid sequences of the head (N-terminal) domains of Type I and Type II trichocyte keratin intermediate filament chains. This has allowed several quasi-repeats to be identified. The secondary structure corresponding to these repeats has been predicted and a model has been produced for key elements of the Type II head domain. Extant disulfide cross-link data have been used as structural constraints. A model for the head domain structure predicts that a twisted beta-sheet region may wrap around the 1A segment and this may reversibly stabilize a coiled-coil conformation for 1A. The evidence in favor of the swinging head model for IF is discussed.

Amino Acid Sequence↗