Rajarshi Chakrabarti | Geisel Medical School at Dartmouth (original) (raw)

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Papers by Rajarshi Chakrabarti

INF2 is a member of the formin family of actin assembly factors. Dominant mis-sense mutations in ... more INF2 is a member of the formin family of actin assembly factors. Dominant mis-sense mutations in INF2 link to two diseases: focal segmental glomerulosclerosis (FSGS), a kidney disease; and Charcot-Marie-Tooth disease (CMTD), a neuropathy. All disease mutations map to the autoinhibitory Diaphanous Inhibitory Domain (DID). Curiously, purified INF2 is not autoinhibited, suggesting the existence of additional cellular inhibitors. We purified an INF2 inhibitor from mouse brain, and identified it as a complex between lysine-acetylated actin (KAc-actin) and cyclase-associated protein (CAP). Inhibition of INF2 by CAP/KAc-actin requires INF2 DID. Treatment of CAP/KAc-actin with histone deacetylase 6 (HDAC6) releases INF2 inhibition, while HDAC6 inhibitors block cellular INF2 activation. INF2 disease mutants are poorly inhibited by CAP/KAc-actin, suggesting that FSGS and CMTD result from reduced CAP/KAc-actin binding. This is the first demonstrated role for lysine-acetylated actin: regulation...

The objective of the present study was to fabricate and monitor real-time, impact of a stable con... more The objective of the present study was to fabricate and monitor real-time, impact of a stable conjugated
linolenic acid, -eleostearic acid (ESA) rich nanoemulsion (NE) formulation (d < 200 nm) vis-à-vis ESA
conventional emulsion (CE) system in ex vivo systems against both endogenous and exogenous reactive
oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was engineered with
the aid of bitter melon seed oil and non-toxic excipients. Morphology and particle size of the emulsion
formulations were studied to validate the stability. The real-time rapid uptake of the ESA NE and its
increased prophylactic efficacy against induced endogenous and exogenous ROS in terms of cell viability
and membrane integrity was evaluated flow-cytometrically and with fluorescence microscopic analysis
of different primary cells.
It was found that the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean diameter,
particle size distribution and zeta potential) for over 12 weeks. Further, ESA NE at a concentration of
∼70 M exhibited maximum efficacy in protecting cells from oxidative damage against both endogenous
and exogenous ROS in lymphocytes and hepatocytes as compared to its corresponding presence in the
CE formulation.
This study provides a real-time empirical evidence on the influence of nano formulation in enhancing
bioavailability and antioxidative properties of ESA.

Journal of Food Science, 2011

Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, ... more Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, Champa, and Kalabou) were analyzed for the content of polyphenol expressed as gallic acid equivalent and flavonoid expressed as quercetein equivalent, and the in vitro total antioxidative activities of the flower extracts were compared with standard and expressed as trolox equivalent. The reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS r + ) scavenging activities, inhibition of lipid peroxidation in a linoleic acid emulsion system, and liposome peroxidation system were measured and compared with respective standard antioxidants. Iron-mediated Fenton reaction was carried out to evaluate the protective effect of the extract of banana flower (Kacha cultivar) against H 2 O 2 -induced DNA damage. The Kacha variety contains the maximum amount of polyphenol (11.94 ± 0.03 mg of GAE/g of dry weight) and flavonoid (0.174 ± 0.001 g of quercetin equivalent/g of polyphenol). It also has the highest total antioxidant capacity, DPPH radical scavenging activity, and ABTS r + radical Q1 scavenging activity with a least EC 50 value of 0.051 mg/mL. Hepatic cell damage in iron-mediated Fenton reaction caused by free radicals is reduced by the banana flower extract. On the basis of the results obtained, the banana flowers are found to be a potential source of natural antioxidants. This is the first report on the antioxidant properties of the extracts from banana flowers. The study suggests that the flowers of M. paradicicus that are found in India and consumed as vegetable can provide valuable functional ingredients that help in the prevention of oxidative stress.

Colloids and surfaces. B, Biointerfaces, Jan 4, 2015

The objective of the present study was to fabricate and monitor real-time, impact of a stable con... more The objective of the present study was to fabricate and monitor real-time, impact of a stable conjugated linolenic acid, α-eleostearic acid (ESA) rich nanoemulsion (NE) formulation (d<200nm) vis-à-vis ESA conventional emulsion (CE) system in ex vivo systems against both endogenous and exogenous reactive oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was engineered with the aid of bitter melon seed oil and non-toxic excipients. Morphology and particle size of the emulsion formulations were studied to validate stability. The real-time rapid uptake of the ESA NE and its increased prophylactic efficacy against induced endogenous and exogenous ROS in terms of cell viability and membrane integrity was evaluated flow-cytometrically and with fluorescence microscopic analysis of different primary cells. It was found that the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean diameter, particle size distribution and zeta potential) for over 12 w...

The objective of the present study was to fabricate and monitor real-time, impact of a stable con... more The objective of the present study was to fabricate and monitor real-time, impact of a stable conjugated linolenic acid,-eleostearic acid (ESA) rich nanoemulsion (NE) formulation (d < 200 nm) vis-à-vis ESA conventional emulsion (CE) system in ex vivo systems against both endogenous and exogenous reac-tive oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was engineered with the aid of bitter melon seed oil and non-toxic excipients. Morphology and particle size of the emulsion formulations were studied to validate stability. The real-time rapid uptake of the ESA NE and its increased prophylactic efficacy against induced endogenous and exogenous ROS in terms of cell viability and membrane integrity was evaluated flow-cytometrically and with fluorescence microscopic analysis of different primary cells. It was found that the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean diameter , particle size distribution and zeta potential) for over 12 weeks. Further, ESA NE at a concentration of ∼70 M exhibited maximum efficacy in protecting cells from oxidative damage against both endogenous and exogenous ROS in lymphocytes and hepatocytes as compared to its corresponding presence in the CE formulation. This study provides a real-time empirical evidence on the influence of nano formulation in enhancing bioavailability and antioxidative properties of ESA.

Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, ... more Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, Champa, and Kalabou) were analyzed for the content of polyphenol expressed as gallic acid equivalent and flavonoid expressed as quercetein equivalent, and the in vitro total antioxidative activities of the flower extracts were compared with standard and expressed as trolox equivalent. The reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS r +) scavenging activities, inhibition of lipid peroxidation in a linoleic acid emulsion system, and liposome peroxidation system were measured and compared with respective standard antioxidants. Iron-mediated Fenton reaction was carried out to evaluate the protective effect of the extract of banana flower (Kacha cultivar) against H 2 O 2-induced DNA damage. The Kacha variety contains the maximum amount of polyphenol (11.94 ± 0.03 mg of gallic acid equivalent/g of dry weight) and flavonoid (0.174 ± 0.001 g of quercetin equivalent/g of polyphenol). It also has the highest total antioxidant capacity, DPPH radical scavenging activity, and ABTS r + radical scavenging activity with a least EC 50 value of 0.051 mg/mL. Hepatic cell damage in iron-mediated Fenton reaction caused by free radicals is reduced by the banana flower extract. On the basis of the results obtained, the banana flowers are found to be a potential source of natural antioxidants. This is the first report on the antioxidant properties of the extracts from banana flowers. The study suggests that the flowers of M. paradicicus that are found in India and consumed as vegetable can provide valuable functional ingredients that help in the prevention of oxidative stress.

Visceral leishmaniasis, a vector-borne tropical disease that is threatening about 350 million peo... more Visceral leishmaniasis, a vector-borne tropical disease that is threatening about 350 million people worldwide, is caused by the protozoan parasite Leishmania donovani. Metalloids like arsenic and antimony have been used to treat diseases like leishmaniasis caused by the kinetoplastid parasites. Arsenic (III) at a relatively higher concentration (30 í µí¼g/mL) has been shown to have antileishmanial activity, but this concentration is reported to be toxic in several experimental mammalian systems. Nanosized metal (0) particles have been shown to be more effective than their higher oxidation state forms. There is no information so far regarding arsenic nanoparticles (As-NPs) as an antileishmanial agent. We have tested the antileishmanial properties of the As-NPs, developed for the first time in our laboratory. As-NPs inhibited the in vitro growth, oxygen consumption, infectivity, and intramacrophage proliferation of L. donovani parasites at a concentration which is about several fold lower than that of As (III). Moreover, this antileishmanial activity has comparatively less cytotoxic effect on the mouse macrophage cell line. It is evident from our findings that As-NPs have more potential than As (III) to be used as an antileishmanial agent.

Background: Cell cycle-specific localization and nuclear function of Phosphatidylinositol-4-phosp... more Background: Cell cycle-specific localization and nuclear function of Phosphatidylinositol-4-phosphate 5-kinase1 (PIP5K) is unclear. Results: SUMOylation of PIP5K at Lys-244 and Lys-490 directs its nuclear entry and its interaction with H3K9me3/HP1-, respectively. Conclusion: PIP5K functions as a member of the rDNA silencing complex. Significance: Our results indicate a possible novel epigenetic role of PIP5K per se in silencing of rDNA.

Phosphatidylinositol 4 phosphate 5 kinase 1a (PIP5K) is mainly localized in the cytosol and plasm... more Phosphatidylinositol 4 phosphate 5 kinase 1a (PIP5K) is mainly localized in the cytosol and plasma membrane. Studies have also indicated its prominent association with nuclear speckles. The exact nature of this nuclear pool of PIP5K is not clear. Using biochemical and microscopic techniques, we have demonstrated that the nuclear pool of PIP5K is modified by SUMO-1 in HEK-293 cells stably expressing PIP5K. Moreover, this SUMOylated pool of PIP5K increased during apoptosis. PolySUMO-2 chain conjugated PIP5K was detected by pull-down experiment using affinity-tagged RNF4, a polySUMO-2 binding protein, during late apoptosis.

Journal of Food Science, 2011

Colloids and surfaces. B, Biointerfaces, Jan 4, 2015

The objective of the present study was to fabricate and monitor real-time, impact of a stable con... more The objective of the present study was to fabricate and monitor real-time, impact of a stable conjugated linolenic acid, α-eleostearic acid (ESA) rich nanoemulsion (NE) formulation (d<200nm) vis-à-vis ESA conventional emulsion (CE) system in ex vivo systems against both endogenous and exogenous reactive oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was engineered with the aid of bitter melon seed oil and non-toxic excipients. Morphology and particle size of the emulsion formulations were studied to validate stability. The real-time rapid uptake of the ESA NE and its increased prophylactic efficacy against induced endogenous and exogenous ROS in terms of cell viability and membrane integrity was evaluated flow-cytometrically and with fluorescence microscopic analysis of different primary cells. It was found that the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean diameter, particle size distribution and zeta potential) for over 12 w...

The objective of the present study was to fabricate and monitor real-time, impact of a stable con... more The objective of the present study was to fabricate and monitor real-time, impact of a stable conjugated linolenic acid,-eleostearic acid (ESA) rich nanoemulsion (NE) formulation (d < 200 nm) vis-à-vis ESA conventional emulsion (CE) system in ex vivo systems against both endogenous and exogenous reac-tive oxygen species (ROS). Accordingly, stable nanoemulsion formulation of ESA was engineered with the aid of bitter melon seed oil and non-toxic excipients. Morphology and particle size of the emulsion formulations were studied to validate stability. The real-time rapid uptake of the ESA NE and its increased prophylactic efficacy against induced endogenous and exogenous ROS in terms of cell viability and membrane integrity was evaluated flow-cytometrically and with fluorescence microscopic analysis of different primary cells. It was found that the fabricated non-toxic ESA NE had stable parameters (hydrodynamic mean diameter , particle size distribution and zeta potential) for over 12 weeks. Further, ESA NE at a concentration of ∼70 M exhibited maximum efficacy in protecting cells from oxidative damage against both endogenous and exogenous ROS in lymphocytes and hepatocytes as compared to its corresponding presence in the CE formulation. This study provides a real-time empirical evidence on the influence of nano formulation in enhancing bioavailability and antioxidative properties of ESA.

Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, ... more Six different cultivars of banana flowers (Musa paradicicus) (Kathali, Bichi, Shingapuri, Kacha, Champa, and Kalabou) were analyzed for the content of polyphenol expressed as gallic acid equivalent and flavonoid expressed as quercetein equivalent, and the in vitro total antioxidative activities of the flower extracts were compared with standard and expressed as trolox equivalent. The reducing power, 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS r +) scavenging activities, inhibition of lipid peroxidation in a linoleic acid emulsion system, and liposome peroxidation system were measured and compared with respective standard antioxidants. Iron-mediated Fenton reaction was carried out to evaluate the protective effect of the extract of banana flower (Kacha cultivar) against H 2 O 2-induced DNA damage. The Kacha variety contains the maximum amount of polyphenol (11.94 ± 0.03 mg of gallic acid equivalent/g of dry weight) and flavonoid (0.174 ± 0.001 g of quercetin equivalent/g of polyphenol). It also has the highest total antioxidant capacity, DPPH radical scavenging activity, and ABTS r + radical scavenging activity with a least EC 50 value of 0.051 mg/mL. Hepatic cell damage in iron-mediated Fenton reaction caused by free radicals is reduced by the banana flower extract. On the basis of the results obtained, the banana flowers are found to be a potential source of natural antioxidants. This is the first report on the antioxidant properties of the extracts from banana flowers. The study suggests that the flowers of M. paradicicus that are found in India and consumed as vegetable can provide valuable functional ingredients that help in the prevention of oxidative stress.