General Information:

Id: 475
Diseases: Parkinson disease
Homo sapiens
BTO:0000138 midbrain; BTO:0000793 SH-SY5Y cell
article
Reference: Zhu JH et al.(2007) Regulation of autophagy by extracellular signal-regulated protein kinases during 1-methyl-4-phenylpyridinium-induced cell death Am. J. Pathol. 170: 75-86 [PMID: 17200184]

Interaction Information:

Comment MPP+-treated cells showed few mitochondria. Instead, the toxin-treated cells exhibited abundant autophagic vacuoles at different stages of evolution.
Formal Description
Interaction-ID: 2205

increases_quantity of

cellular component

autophagic vacuole

Comment MPP+-treated cells showed few mitochondria. Instead, the toxin-treated cells exhibited abundant autophagic vacuoles at different stages of evolution.
Formal Description
Interaction-ID: 2206

decreases_quantity of

cellular component

mitochondrion

Comment MPP+-treatment elicit significantly increased levels of the membrane-bound LC3 form. LC3 conjugation to the autophagic vesicle membrane is required for initiation of autophagy.
Formal Description
Interaction-ID: 2208

gene/protein

MAP1LC3A

affects_activity of

process

autophagy

Comment MPP+-treatment induces autophagic mitochondrial degradation. MPP+ elicited the appearance of granular LC3 staining in TH neurons, indicative of autophagy.
Formal Description
Interaction-ID: 2210

increases_activity of

process

macroautophagy

Comment Beclin1 associates with the class III PI3K to induce autophagy. Knockdown of Beclin 1 expression using RNA interference failed to inhibit MPP+-induced autophagy.
Formal Description
Interaction-ID: 2211

gene/protein

BECN1

increases_activity of

process

autophagy

Comment Inhibitors of the upstream ERK kinase MEK, like UO126, effectively suppressed the autophagic response to MPP+ injury.
Formal Description
Interaction-ID: 2212

drug/chemical compound

U0126

decreases_activity of

gene/protein

MAP2K1

Drugbank entries Show/Hide entries for MAP2K1
Comment Inhibitors of the upstream ERK kinase MEK, like UO126, effectively suppressed the autophagic response to MPP+ injury.
Formal Description
Interaction-ID: 2213

drug/chemical compound

U0126

decreases_activity of

process

autophagy

if autophagy has been induced by MPP treatment
Comment Inhibitors of the upstream ERK kinase MEK, like UO126, effectively suppressed the autophagic response to MPP+ injury.
Formal Description
Interaction-ID: 2214

drug/chemical compound

U0126

decreases_quantity of

cellular component

autophagic vacuole

if autophagy has been induced by MPP treatment
Comment MEK inhibitors, like UO126, that reduce MPP+-induced autophagic vesicles, conferred significant protection from MPP+ toxicity. As observed in SH-SY5Y cells, MEK inhibition conferred protection from MPP+ in primary midbrain TH neurons.
Formal Description
Interaction-ID: 2215

drug/chemical compound

U0126

decreases_activity of

process

neuron death

if cell death has been induced by MPP
Comment Increased phosphorylation of ERK was observed beginning 8 hours after MPP+ administration. Increased shift of membrane-bound LC3 was observed 16 hours after MPP+ administration.
Formal Description
Interaction-ID: 2216

increases_phosphorylation of

gene/protein

MAPK3

Drugbank entries Show/Hide entries for MAPK3
Comment Knockdown of LC3 with siRNA showed significant protection of cells from MPP+-induced toxicity. Moreover, siRNA knockdown of Atg5 and Atg7, two other proteins involved in membrane conjugation necessary for initiating autophagy, also showed significant protection from cell death.
Formal Description
Interaction-ID: 2217

gene/protein

MAP1LC3A

affects_activity of

process

neuron death

if cell death has been induced by MPP
Comment Knockdown of LC3 with siRNA showed significant protection of cells from MPP+-induced toxicity. Moreover, siRNA knockdown of Atg5 and Atg7, two other proteins involved in membrane conjugation necessary for initiating autophagy, also showed significant protection from cell death.
Formal Description
Interaction-ID: 2218

gene/protein

ATG5

affects_activity of

process

neuron death

if cell death has been induced by MPP
Comment Knockdown of LC3 with siRNA showed significant protection of cells from MPP+-induced toxicity. Moreover, siRNA knockdown of Atg5 and Atg7, two other proteins involved in membrane conjugation necessary for initiating autophagy, also showed significant protection from cell death.
Formal Description
Interaction-ID: 2219

gene/protein

ATG7

affects_activity of

process

neuron death

if cell death has been induced by MPP
Comment Beclin1 associates with the class III PI3K to induce autophagy. Knockdown of Beclin 1 expression using RNA interference failed to inhibit MPP+-induced autophagy.
Formal Description
Interaction-ID: 2342

gene/protein

BECN1

interacts (colocalizes) with

gene/protein

PIK3C3

Drugbank entries Show/Hide entries for PIK3C3