Publications by authors named "Mohan Sreelekshmi"

4 Publications

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Vanillic acid mitigates the impairments in glucose metabolism in HepG2 cells through BAD-GK interaction during hyperinsulinemia.

J Biochem Mol Toxicol 2021 Mar 2:e22750. Epub 2021 Mar 2.

Biochemistry and Molecular Mechanism Laboratory, Agro-processing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, Kerala, India.

Glucokinase (GK), a key regulator of hepatic glucose metabolism in the liver and glucose sensor and mediator in the secretion of insulin in the pancreas, is not studied in detail for its therapeutic application in diabetes. Herein, we study the alteration in GK activity during hyperinsulinemia-induced insulin resistance in HepG2 cells. We also investigated the link between GK and Bcl-2-associated death receptor (BAD) during hyperinsulinemia. There are emerging demands for GK activators from natural resources, and we selected vanillic acid (VA) to evaluate its potential as GK activators during hyperinsulinemia in HepG2 cells. VA is a phenolic compound and a commonly used food additive in many food industries. We found that VA safeguarded GK inhibition during hyperinsulinemia significantly in HepG2 cells. VA also prevented the depletion of glycogen synthesis during hyperinsulinemia, which is evident from protein expression studies of phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, glycogen synthase, and glycogen synthase kinase-3β. This was associated with activation of BAD activity, which was also confirmed by Western blotting. Molecular docking revealed strong binding between GK active site and VA, supporting their strong interaction. These are the first in vitro data to indicate the beneficial properties of VA with respect to insulin resistance induced by hyperinsulinemia by GK activation. Since it is activated via BAD, the hypoglycemia associated with general GK activation is not expected here and therefore has significant implications for future therapies against diabetes.
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http://dx.doi.org/10.1002/jbt.22750DOI Listing
March 2021

Corrigendum to "Chlorogenic acid attenuates glucotoxicity in H9c2 cells via inhibition of glycation and PKC α upregulation and safeguarding innate antioxidant status" [Biomed. Pharmacother. 100 (2018) 467-477].

Biomed Pharmacother 2021 Jan 6;133:111071. Epub 2020 Dec 6.

Biochemistry and Molecular Mechanism Laboratory, Agro-Processing and Technology Division, CSIR- National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India; Academy of Scientific and Innovative Research (AcSIR), CSIR-HRDC Campus, Ghaziabad, Uttar Pradesh, 201 002, India. Electronic address:

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http://dx.doi.org/10.1016/j.biopha.2020.111071DOI Listing
January 2021

Endoplasmic reticulum stress: A master regulator of metabolic syndrome.

Eur J Pharmacol 2019 Oct 17;860:172553. Epub 2019 Jul 17.

Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Industrial Estate, Thiruvananthapuram, 695019, Kerala, India; Academy of Scientific & Innovative Research (AcSIR), New Delhi, India. Electronic address:

Endoplasmic reticulum (ER) stress, a change in the ER homeostasis, leads to initiation of the unfolded protein response (UPR). The primary functions of the UPR are to restore the ER's physiological activity and coordinate the apoptotic and adaptive responses. Pathophysiological conditions that augment ER stress include hypoxia, misfolded and/or mutated protein accumulation, and high glucose. Prolonged ER stress is a critical factor in the pathogenesis of metabolic syndrome including type 2 diabetes mellitus, cardiovascular diseases, atherosclerosis, obesity, and fatty liver disease. UPR is a complex homeostatic pathway between newly synthesized proteins and their maturation, although the regulatory mechanisms contributing to the UPR and the possible therapeutic strategies are yet to be clarified. Therefore, a comprehensive understanding of the underlying molecular mechanisms is necessary to develop therapeutic interventions targeting ER stress response. In this review, we discuss the role of ER stress and UPR signaling in the pathogenesis of metabolic syndrome, highlighting the main functions of UPR components. We have emphasized the use of novel small molecular chemical chaperones, considered as modulators of ER stress. The initial studies with these chemical chaperones are promising, but detailed studies are required to define their efficacy and adverse effects during therapeutic use in humans.
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http://dx.doi.org/10.1016/j.ejphar.2019.172553DOI Listing
October 2019

Chlorogenic acid attenuates glucotoxicity in H9c2 cells via inhibition of glycation and PKC α upregulation and safeguarding innate antioxidant status.

Biomed Pharmacother 2018 Apr 23;100:467-477. Epub 2018 Feb 23.

Biochemistry and Molecular Mechanism Laboratory, Agroprocessing and Technology Division, CSIR-National Institute for Interdisciplinary Science and Technology, Thiruvananthapuram, 695019, Kerala, India. Electronic address:

A series of cardiovascular complications associated with hyperglycemia is a critical threat to the diabetic population. Here we elucidate the link between hyperglycemia and cardiovascular diseases onset, focusing on oxidative stress and associated cardiac dysfunctions. The contribution of advanced glycation end products (AGE) and protein kinase C (PKC) signaling is extensively studied. For induction of hyperglycemia, H9c2 cells were incubated with 33 mM glucose for 48 h to simulate the diabetic condition in in vitro system. Development of cardiac dysfunction was confirmed with the significant increase of lactate dehydrogenase (LDH) release to the medium and associated decrease in cell viability. Various parameters like free radical generation, alteration in innate antioxidant system, lipid peroxidation, AGE production and PKC α -ERK axis were investigated during hyperglycemia and with chlorogenic acid. Hyperglycemia has significantly enhanced reactive oxygen species (ROS- 4 fold) generation, depleted SOD activity (1.3 fold) and expression of enzymes particularly CuZnSOD (SOD1) and MnSOD (SOD2), increased production of AGE (2.18 fold). Besides, PKC α dependent ERK signaling pathway was found activated (1.43 fold) leading to cardiac dysfunction during hyperglycemia. Chlorogenic acid (CA) was found beneficial against hyperglycemia most probably through its antioxidant mediated activity. The outcome of this preliminary study reveals the importance of integrated approach emphasizing redox status, glycation and signaling pathways like PKC α - ERK axis for control and management of diabetic cardiomyopathy (DCM) and potential of bioactives like CA.
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http://dx.doi.org/10.1016/j.biopha.2018.02.027DOI Listing
April 2018