Biomedical subjects

Maryam Taheri

Publications and source records attributed to Maryam Taheri.

3 recordsLinked to original sources

PubMed2004

The ER glycoprotein quality control system.

The endoplasmic reticulum (ER) is the major site for folding and sorting of newly synthesized secretory cargo proteins. One central regulator of this process is the quality control machinery, which retains and ultimately disposes of misfolded secretory proteins before they can exit the ER. The ER quality control process is highly effective and mutations in cargo molecules are linked to a variety of diseases. In mammalian cells, a large number of secretory proteins, whether membrane bound or soluble, are asparagine (N)-glycosylated. Recent attention has focused on a sugar transferase, UDP-Glucose: glycoprotein glucosyl transferase (UGGT), which is now recognized as a constituent of the ER quality control machinery. UGGT is capable of sensing the folding state of glycoproteins and attaches a single glucose residue to the Man9GlcNAc2 glycan of incompletely folded or misfolded glycoproteins. This enables misfolded glycoproteins to rebind calnexin and reenter productive folding cycles. Prolonging the time of glucose addition on misfolded glycoproteins ultimately results in either the proper folding of the glycoprotein or its presentation to an ER associated degradation machinery.

Amino Acid Sequence↗

PubMed2003

The adhesion and differentiation-inhibitory activities of the immunoglobulin superfamily member, carcinoembryonic antigen, can be independently blocked.

The external domains of Ig superfamily members are involved in multiple binding interactions, both homophilic and heterophilic, that initiate molecular events leading to the execution of diverse cell functions. Human carcinoembryonic antigen (CEA), an Ig superfamily cell surface glycoprotein used widely as a clinical tumor marker, undergoes homophilic interactions that mediate intercellular adhesion. Recent evidence supports the view that deregulated overexpression of CEA has an instrumental role in tumorigenesis through the inhibition of cell differentiation and the disruption of tissue architecture. The CEA-mediated block of the myogenic differentiation of rat L6 myoblasts depends on homophilic binding of its external domains. We show here that L6 transfectant cells expressing CEA can "trans-block" the myogenesis of juxtaposed differentiation-competent L6 transfectant cells expressing a deletion mutant of CEA (DeltaNCEA). This result implies the efficacy of antiparallel CEA-CEA interactions between cells in the differentiation block. In addition, DeltaNCEA can acquire differentiation blocking activity by cross-linking with specific anti-CEA antibodies, thus implying the efficacy of parallel CEA-CEA interactions on the same cell surface. The myogenic differentiation blocking activity of CEA was demonstrated by site-directed mutations to involve three subdomains of the amino-terminal domain, shown previously to be critical for its intercellular adhesion function. Monovalent Fab fragments of monoclonal antibodies binding to the region bridging subdomains 1 and 2 could both inhibit intercellular adhesion and release the myogenic differentiation block. Amino acid substitutions Q80A, Q80R, and D82N in subdomain 3, QNDTG, however, were found to completely ablate the differentiation blocking activity of CEA but had no effect on intercellular adhesion activity. A cyclized peptide representing this subdomain was the most effective at releasing the differentiation block.

Amino Acid Substitution↗

PubMedDate not supplied

The salutary effects of antioxidant vitamins on the plasma lipids of healthy middle aged-to-elderly individuals: a randomized, double-blind, placebo-controlled study.

STUDY OBJECTIVE: To determine the efficacy of antioxidant vitamins C and E in lowering the serum lipid levels in apparently healthy middle aged-to-elderly subjects. DESIGN: Randomized, double-blind, placebo-controlled trial. SETTING: University outpatient clinic. PARTICIPANTS: One hundred twenty subjects (60 males and 60 females) with no known cardiovascular disease, aged 50 and over were enrolled into the study and were randomly allocated to four age and sex matched groups. Each group was subsequently randomized to receive vitamin C, vitamin E, their combination and placebo respectively, for 75 days. Pre-and post-treatment fasting plasma lipid profiles were determined for each case. RESULTS: Except for serum triglyceride level which did not change significantly in group "A" cases receiving vitamin C, there was a quite significant reduction in the serum levels of total cholesterol, LDL-C and triglyceride in all treatment groups compared to the placebo (P < 0.001). CONCLUSION: Antioxidant vitamins C and E or their combination can effectively lower the serum cholesterol and LDL levels and raise the serum HDL level in the middle aged-to-elderly healthy individuals.

Aged↗