Mind map

Endoplasmic Reticulum

Katerine Caicedo Spanish

Map content

Smooth ER
- No ribosomes
- Lipid and steroid metabolism
- Drug detoxification
- Calcium storage
Rough ER
- Large amount of ribosomes
- Protein synthesis
- Intracellular transport
- Post-translational protein modifications
Cell membrane system
- Flattened and tubular sacs
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
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