Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P11021 (BiP)
 2,049 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cholera toxin (CT) contains one A chain and five B chains. The A chain is an enzyme that covalently modifies a trimeric G protein in the cytoplasm, resulting in the overproduction of cAMP. The B chain binds the glycosphingolipid G(M1), the cell surface receptor for CT, which initiates receptor-mediated endocytosis of the toxin. After endocytosis, CT enters the endoplasmic reticulum (ER) via retrograde vesicular traffic where the A chain retro-translocates through the ER membrane to reach the cytoplasm. The retro-translocation mechanism is poorly understood, but may involve proteins of the ER stress response, including the ER associated degradation (ERAD) pathway. We report here that treating cells with CT or CTB quickly up-regulates the levels of BiP, Derlin-1, and Derlin-2, known participants in the ER stress response and ERAD. CT did not induce calnexin, another known responder to ER stress, indicating that the CT-mediated induction of ER proteins is selective in this time frame. These data suggest that CT may promote retro-translocation of the A chain to the cytoplasm by rapidly up-regulating a set of ER proteins involved in the retro-translocation process. In support of this idea, a variety of conditions that induced BiP, Derlin-1, and Derlin-2 sensitized cells to CT and conditions that inhibited their induction de-sensitized cells to CT. Moreover, specifically suppressing Derlin-1 with siRNA protected cells from CT. In addition, Derlin-1 co-immunoprecipitated with CTA or CTB from CT-treated cells using anti-CTA or anti-CTB antibodies. Altogether, the results are consistent with the hypothesis that the B chain of CT up-regulates ER proteins that may assist in the retro-translocation of the A chain across the ER membrane.
 ...
PMID:Cholera toxin up-regulates endoplasmic reticulum proteins that correlate with sensitivity to the toxin. 1822 71

The endoplasmic reticulum chaperone and stress protein BiP has hitherto been considered as having only crucial intracellular cell protective functions. However, we have shown that BiP can be present in the extracellular environment and that it binds to a putative but as yet uncloned cell surface receptor. It will stimulate human monocytes via this receptor to express a gene profile that is anti-inflammatory. It will generate T cells with a regulatory function from human peripheral blood most likely by altering dendritic cell development. Intravenous BiP will both prevent and treat ongoing collagen induced arthritis in the DBA/1 mouse. Part of the suppression of arthritis is linked to interleukin (IL)4 as BiP-specific lymph node and spleen cells from these mice secrete IL4, and BiP has no suppressive effect on collagen induced arthritis in IL4 knockout mice. Lymph node and spleen cells isolated from mice administered intravenous BiP will suppress arthritis when transferred intravenously into recipient arthritic mice without any further BiP having to be given. Thus, both in vitro work with human peripheral blood mononuclear cells and in vivo work in the collagen arthritis model lead to the conclusion that BiP induces regulatory cells. Finally, intravenous BiP will ablate the inflammatory cell infiltrate and inflammatory cytokine expression in rheumatoid synovial membrane tissue transplanted subcutaneously into SCID mice. The conclusion from all this experimental work is that BiP may be a novel therapy for the treatment of patients with rheumatoid arthritis.
 ...
PMID:BiP, an anti-inflammatory ER protein, is a potential new therapy for the treatment of rheumatoid arthritis. 1857 76

Aging is an important factor affecting the deterioration of patients with coronavirus disease 2019 (COVID-19). The aging and degeneration of various tissues and organs in the elderly lead to impaired organ function. Underlying conditions such as chronic lung disease, cardiovascular disease, and diabetes in aged patients are associated with higher mortality. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) primarily interacts with the cell surface receptor angiotensin-converting enzyme (ACE) 2 and other accessory proteins such as 78 kDa glucose-regulated protein 78 (GRP78) and CD147. Thus, altered receptor signals in aging and chronic disease play a role in SARS-CoV-2 infection, and are associated with a higher risk of deterioration in different organs. In this review, after a brief introduction to the link between aging and receptors for SARS-CoV-2, we focus on the risk of deterioration in different organs of COVID-19 patients considering aging as the main factor. We further discuss the structural and/or physiological changes in the immune system and organs (lung, heart, kidney, vessels, nerve system), as well as those associated with diabetes, in aging patients, and speculate on the most likely mechanisms underlying the deterioration of COVID-19 patients.
 ...
PMID:Influence of aging on deterioration of patients with COVID-19. 3323 72