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Phenolic‐rich extract of avocado Persea americana (var. Colinred) peel blunts paraquat/maneb‐induced apoptosis through blocking phosphorylation of LRRK2 kinase in human nerve‐like cells
It is increasingly evident that LRRK2 kinase activity is involved in oxidative stress (OS)‐induced apoptosis—a type of regulated cell death and neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that a phenolic‐rich extract of avocado Persea americana var. Colinred peel (CRE, 0.01 mg/ml) restricts environmental neurotoxins paraquat (1 mM)/maneb (0.05 mM)‐induced apoptosis process through blocking reactive oxygen species (ROS) signaling and concomitant inhibition of phosphorylation of LRRK2 in nerve‐like cells (NLCs). Indeed, PQ + MB at 6 h exposure significantly increased ROS (57 ± 5%), oxidation of protein DJ‐1cys106SOH into DJ‐1Cys106SO3 ([~3.7 f(old)‐(i)ncrease]), augmented p‐(S935)‐LRRK2 kinase (~20‐f(old) (i)ncrease), induced nuclei condensation/fragmentation (28 ± 6%), increased the expression of PUMA (~6.2‐fi), and activated CASPASE‐3 (CASP‐3, ~4‐fi) proteins; but significantly decreased mitochondrial membrane potential (ΔΨm, ~48 ± 4%), all markers indicative of apoptosis compared to untreated cells. Remarkably, CRE significantly diminished both OS‐signals (i.e., DCF+ cells, DJ‐1Cys106SO3) as well as apoptosis markers (e.g., PUMA, CASP‐3, loss of ΔΨm, p‐LRRK2 kinase) in NLCs exposed to PQ + MB. Furthermore, CRE dramatically reestablishes the transient intracellular Ca2+ flow (~300%) triggered by dopamine (DA) in neuronal cells exposed to PQ + MB. We conclude that PQ + MB‐induced apoptosis in NLCs through OS‐mechanism, involving DJ‐1, PUMA, CASP‐3, LRRK2 kinase, mitochondria damage, DNA fragmentation, and alteration of DA‐receptors. Our findings imply that CRE protects NLCs directly via antioxidant mechanism and indirectly by blocking LRRK2 kinase against PQ + MB stress stimuli. These data suggest that CRE might be a potential natural antioxidant.
Phenolic‐rich extract of avocado Persea americana (var. Colinred) peel blunts paraquat/maneb‐induced apoptosis through blocking phosphorylation of LRRK2 kinase in human nerve‐like cells
It is increasingly evident that LRRK2 kinase activity is involved in oxidative stress (OS)‐induced apoptosis—a type of regulated cell death and neurodegeneration, suggesting LRRK2 inhibition as a potential therapeutic target. We report that a phenolic‐rich extract of avocado Persea americana var. Colinred peel (CRE, 0.01 mg/ml) restricts environmental neurotoxins paraquat (1 mM)/maneb (0.05 mM)‐induced apoptosis process through blocking reactive oxygen species (ROS) signaling and concomitant inhibition of phosphorylation of LRRK2 in nerve‐like cells (NLCs). Indeed, PQ + MB at 6 h exposure significantly increased ROS (57 ± 5%), oxidation of protein DJ‐1cys106SOH into DJ‐1Cys106SO3 ([~3.7 f(old)‐(i)ncrease]), augmented p‐(S935)‐LRRK2 kinase (~20‐f(old) (i)ncrease), induced nuclei condensation/fragmentation (28 ± 6%), increased the expression of PUMA (~6.2‐fi), and activated CASPASE‐3 (CASP‐3, ~4‐fi) proteins; but significantly decreased mitochondrial membrane potential (ΔΨm, ~48 ± 4%), all markers indicative of apoptosis compared to untreated cells. Remarkably, CRE significantly diminished both OS‐signals (i.e., DCF+ cells, DJ‐1Cys106SO3) as well as apoptosis markers (e.g., PUMA, CASP‐3, loss of ΔΨm, p‐LRRK2 kinase) in NLCs exposed to PQ + MB. Furthermore, CRE dramatically reestablishes the transient intracellular Ca2+ flow (~300%) triggered by dopamine (DA) in neuronal cells exposed to PQ + MB. We conclude that PQ + MB‐induced apoptosis in NLCs through OS‐mechanism, involving DJ‐1, PUMA, CASP‐3, LRRK2 kinase, mitochondria damage, DNA fragmentation, and alteration of DA‐receptors. Our findings imply that CRE protects NLCs directly via antioxidant mechanism and indirectly by blocking LRRK2 kinase against PQ + MB stress stimuli. These data suggest that CRE might be a potential natural antioxidant.
Phenolic‐rich extract of avocado Persea americana (var. Colinred) peel blunts paraquat/maneb‐induced apoptosis through blocking phosphorylation of LRRK2 kinase in human nerve‐like cells
Quintero‐Espinosa, Diana A. (author) / Ortega‐Arellano, Hector Flavio (author) / Velez‐Pardo, Carlos (author) / Jimenez‐Del‐Rio, Marlene (author)
Environmental Toxicology ; 37 ; 660-676
2022-03-01
17 pages
Article (Journal)
Electronic Resource
English
avocado , LRRK2 , neurodegeneration , oxidative stress , Parkinson , PF‐06447475 , paraquat , Colinred , maneb
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