Endoplasmic Reticulum

Endoplasmic Reticulum

1. Smooth ER

   • No ribosomes
   • Lipid and steroid metabolism
   • Drug detoxification
   • Calcium storage

2. Rough ER

   • Large amount of ribosomes
   • Protein synthesis
   • Intracellular transport
   • Post-translational protein modifications

3. Cell membrane system

   • Flattened and tubular sacs

4. ER Stress

   • molecular changes that alterate ER homeostasis
     • hypoxia
     • free radicals
     • inflammation
     • drugs toxicity
     • unfolded or misfolded proteins
       • Unfolded protein response
         • degrades misfolded proteins
         • restores normal function
         • activates production of chaperones
         • failure of these mechanisms lead to apoptosis
     • reversible or irreversible injuries

5. Endoplasmic Reticulum Stress

   • Chronic Kidney Disease
     • metabolic and haemodynamic perturbations
       • ER stress
         • cell death
           • activation of PERK/ATF4F pathway
             • tubular apoptosis
             • renal lesions
         • fibrosis
           • TGF-B1 participation
             • induces profibrotic factors
             • induces ER stress markers
             • inhibited by chaperones
           • epithelial to mesenchymal transition
             • profibotic process
               • deposition of ECM
                 • requieres sXB1
               • secretion of mediators
         • chronic inflammation
           • IRE1α signaling
             • TRAF and AP1-
               • proinflammatory pathways activation
                 • NF KB
                 • NOD 1/2
                 • RIP-dependent cascades
           • PERK signaling
             • increased NFKB stability
               • proinflammatory macrophague polarization
           • ER stress-induced proinflammatory cytokines
             • IL4B
             • IL18
   • Interventions
     • GLP-1 receptor agonists
       • modulate
         • XBP4 splicing and CHOP
         • PERK/elF2or arm
         • ATF4 transcription
     • chemical chaperones
       • 4PBA
         • correction of haemodynamic perturbations
         • modulates
           • inflammatory cascade
           • aristolochic acid-induced UPR response
           • PERK - eIF2α pathway
             • protects from hypid-mediated injury
             • ameloration of renal function
       • UDCA
         • inhibitis UPR response
         • inhibitis ER stress
     • ER proteins modulation
       • RTN1 knockdown
         • reduces
           • hyperglucaemia-induced ER stress
           • apoptosis
         • inhibition of its interaction with PERK
       • overexpression of sNogo-β
         • prevents Nogo-β downregulation
           • modulation of PERK/ATF4/ATF6
           • ameliorates diabetic kidney disease
     • flavonoids
       • chrysin
         • inhibition of ER stress
           • No PERK/apoptosis pathway
   • Unfolded protein response
     • IRE1α
       • TRAF2/ASK1 complex
         • JNK and p38 activation
           • apoptosis
       • XBP1 mRNA cleavage
         • spliced xBP1
           • ERAD
           • Chaperone and lypid synthesis
           • glicosylation
       • RIDD
         • RNA degradation
     • PERK
       • elF2α
         • ATF4 activation
           • CHOP signaling
             • apoptosis
           • negative regulation by
             • GADD34
             • PP1C
         • NRF2 activation
           • antioxidant responses
     • ATF6
       • cleaved in golgi
         • release of transcription factor
           • ERAD and CHOP
           • chaperone expression
           • ER stress response elements

Imagens e arquivos do mapa